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Clinical Trial Results:
A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination with Rituximab (R) Or Obinutuzumab (G) Plus Bendamustine (B) In Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

Summary
EudraCT number	2014-001361-28
Trial protocol	CZ HU DE GB ES NL FR IT
Global end of trial date	21 Oct 2021

Results information
Results version number	v1(current)
This version publication date	03 Nov 2022
First version publication date	03 Nov 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GO29365

ISRCTN number

US NCT number

NCT02257567

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland,

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, + 41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, + 41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

21 Oct 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Oct 2021

Was the trial ended prematurely?

Main objective of the trial

This study was a multicentre, open-label study of polatuzumab vedotin (Pola) administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprised two stages: a Phase Ib safety run-in stage and a Phase II stage.

Protection of trial subjects

All participants were required to sign the informed consent form (ICF).

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Oct 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety

Long term follow-up duration

7 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 29

Country: Number of subjects enrolled

Canada: 44

Country: Number of subjects enrolled

Czechia: 20

Country: Number of subjects enrolled

France: 26

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Hungary: 14

Country: Number of subjects enrolled

Italy: 11

Country: Number of subjects enrolled

Korea, Republic of: 20

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

Spain: 32

Country: Number of subjects enrolled

Turkey: 19

Country: Number of subjects enrolled

United Kingdom: 17

Country: Number of subjects enrolled

United States: 95

Worldwide total number of subjects

331

EEA total number of subjects

107

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

133

From 65 to 84 years

191

85 years and over

Subject disposition

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Recruitment details

A total of 331 were enrolled in this study at 56 investigative sites in the following countries: Australia, Canada, Czech Republic, France, Germany, Hungary, Italy, Korea, the Netherlands, Spain, Turkey, United Kingdom, and the United States from 15 October 2014 to 20 October 2021.

Screening details

Participants were enrolled in Phase Ib and Phase II to receive polatuzumab vedotin (liquid formulation in randomised & expansion stages; lyophilized in new formulation (NF) cohorts) in combination with standard doses of BG and BR. Out of 331 participants, 327 participants received at least one dose of study drug and their intended treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL

Arm description

Participants with FL received pola, 1.8 milligrams per kilogram (mg/kg), as intravenous (IV) infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 milligrams per meter-squared (mg/m^2), as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab, 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL

Arm description

Participants with DLBCL received pola 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine, 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab, 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL

Arm description

Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and obinutuzumab 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

GA101; Gazyva; Gazyvaro

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Obinutuzumab, 1000 mg, administered as IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL

Arm description

Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and obinutuzumab 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

GA101; Gazyva; Gazyvaro

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Obinutuzumab, 1000 mg, administered as IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Arm A (Phase II Randomisation): Pola+BR in FL

Arm description

Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab, 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Arm B (Phase II Randomisation): BR in FL

Arm description

Participants with FL received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1 (each cycle is 28 days), thereafter on Days 1 and 2 of Cycles 2 to 6 in combination with rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6.

Arm type

Active comparator

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab, 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Arm C (Phase II Randomisation): Pola+BR in DLBCL

Arm description

Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab, 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Arm D (Phase II Randomisation): BR in DLBCL

Arm description

Participants with DLBCL received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1 (each cycle is 21 days), thereafter on Days 1 and 2 of Cycles 2 to 6 in combination with rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6.

Arm type

Active comparator

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab , 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Arm E (Phase II Expansion): Pola+BG in FL

Arm description

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

GA101; Gazyva; Gazyvaro

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Obinutuzumab, 1000 mg, administered as IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Arm F (Phase II Expansion): Pola+BG in DLBCL

Arm description

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

GA101; Gazyva; Gazyvaro

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Obinutuzumab, 1000 mg, administered as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6.

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Arm description

Participants with DLBCL received pola (lyophilized formulation), 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

Other name

DCDS4501A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pola 1.8 mg/kg, administered as IV infusion on Day 2 of Cycle 1, and thereafter on Day 1 of Cycles 2 to 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan; MabThera

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab, 375 mg/m^2, administered as IV on Day 1 of each cycle for up to 6 cycles.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda; Ribomustin; Levact

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 90 mg/m^2, per day administered as IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of Cycle 2 to 6.

Number of subjects in period 1	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Started	6	6	6	6	39	41	40	40	20	21	106
Safety Population	6	6	6	6	38	41	39	39	20	20	106
Completed	4	4	2	1	20	22	6	2	16	0	30
Not completed	2	2	4	5	19	19	34	38	4	21	76
Adverse event, serious fatal	2	2	2	4	15	11	26	30	2	18	65
Consent withdrawn by subject	-	-	2	-	-	6	6	6	1	1	10
Physician decision	-	-	-	-	-	-	-	2	-	1	-
Not treated/Didn'tContinue	-	-	-	-	1	-	2	-	-	-	-
Adverse event, non-fatal	-	-	-	1	1	-	-	-	1	-	-
Lost to follow-up	-	-	-	-	2	2	-	-	-	1	1

Baseline characteristics

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Reporting group title

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL

Reporting group description

Reporting group title

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL

Reporting group description

Reporting group title

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL

Reporting group description

Reporting group title

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL

Reporting group description

Reporting group title

Arm A (Phase II Randomisation): Pola+BR in FL

Reporting group description

Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Arm B (Phase II Randomisation): BR in FL

Reporting group description

Reporting group title

Arm C (Phase II Randomisation): Pola+BR in DLBCL

Reporting group description

Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Arm D (Phase II Randomisation): BR in DLBCL

Reporting group description

Reporting group title

Arm E (Phase II Expansion): Pola+BG in FL

Reporting group description

Reporting group title

Arm F (Phase II Expansion): Pola+BG in DLBCL

Reporting group description

Reporting group title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Reporting group description

Reporting group values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL	Total
Number of subjects	6	6	6	6	39	41	40	40	20	21	106	331
Age categorical
Units: Subjects
Age Continuous
Units: years
median (full range (min-max))	68.0 (54 to 73)	65.0 (58 to 79)	63.5 (42 to 73)	71.0 (53 to 84)	65.0 (37 to 74)	63.0 (39 to 80)	67.0 (33 to 86)	71.0 (30 to 84)	60.5 (37 to 86)	65.0 (26 to 86)	70.0 (24 to 94)	-
Sex: Female, Male
Units: Participants
Female	4	2	2	1	18	23	12	15	10	10	54	151
Male	2	4	4	5	21	18	28	25	10	11	52	180
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	1	0	0	0	1
Asian	1	1	0	0	1	2	6	4	1	6	8	30
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	1	0	3	0	2	0	1	7
White	5	5	6	6	33	33	26	31	16	15	83	259
More than one race	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	4	6	5	4	1	0	14	34
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	0	0	0	0	1	3	1	1	3	2	3	14
Not Hispanic or Latino	6	6	6	6	34	34	35	36	16	19	87	285
Not Stated	0	0	0	0	2	3	3	1	0	0	13	22
Unknown	0	0	0	0	2	1	1	2	1	0	3	10

End points

Top of page

Reporting group title

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL

Reporting group description

Reporting group title

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL

Reporting group description

Reporting group title

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL

Reporting group description

Reporting group title

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL

Reporting group description

Reporting group title

Arm A (Phase II Randomisation): Pola+BR in FL

Reporting group description

Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Arm B (Phase II Randomisation): BR in FL

Reporting group description

Reporting group title

Arm C (Phase II Randomisation): Pola+BR in DLBCL

Reporting group description

Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Arm D (Phase II Randomisation): BR in DLBCL

Reporting group description

Reporting group title

Arm E (Phase II Expansion): Pola+BG in FL

Reporting group description

Reporting group title

Arm F (Phase II Expansion): Pola+BG in DLBCL

Reporting group description

Reporting group title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Reporting group description

Subject analysis set title

Arm G (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm H (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm H (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Arm G (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm G (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm G (Phase II NF Cohort): Pola+BR in DLBCL

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Phase Ib: Percentage of Participants with Adverse Events (AEs)

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End point title

Phase Ib: Percentage of Participants with Adverse Events (AEs) ^[1] ^[2]

End point description

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Safety population consisted of all ITT participants in Phase Ib who received at least one dose of study medication.

End point type

Primary

End point timeframe

From the study start up to the end of the study (up to approximately 84 months)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL
Number of subjects analysed	6	6	6	6
Units: percentage of participants
number (not applicable)	100	100	100	100

No statistical analyses for this end point

Primary: Arm G+H (Phase II NF Cohort): Percentage of Participants with AEs

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End point title

Arm G+H (Phase II NF Cohort): Percentage of Participants with AEs ^[3] ^[4]

End point description

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. Safety population consisted of all ITT participants from Arm G and H (Phase II NF Cohort) who received at least one dose of study medication.

End point type

Primary

End point timeframe

From Month 37 to Month 84 (up to approximately 47 months)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for NF cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arm G and H, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: percentage of participants
number (not applicable)	99.1

No statistical analyses for this end point

Primary: Cohort 1a (Phase Ib): Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin

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End point title

Cohort 1a (Phase Ib): Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin ^[5] ^[6]

End point description

The number of participants with positive results for ADA against pola at Baseline & at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline timepoints were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA=negative or missing baseline ADA result(s) & at least one positive post-baseline ADA result. Treatment-enhanced ADA=a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs & treatment enhanced ADAs. Values have been rounded off to the nearest whole number. Safety population consisted of all ITT participants from Cohort 1a (Phase Ib) who received at least one dose of study medication.

End point type

Primary

End point timeframe

Baseline up to approximately Month 24

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for Phase Ia cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Cohort 1a, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL
Number of subjects analysed	6	6
Units: percentage of participants
number (not applicable)
Baseline Prevalence of ADAs	50.0	33.3
Post-Baseline Incidence of ADAs	0	33.3

No statistical analyses for this end point

Primary: Cohort 1b (Phase Ib): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

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End point title

Cohort 1b (Phase Ib): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab ^[7] ^[8]

End point description

Number of participants with positive results for ADA against pola at Baseline & at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline timepoints=post-baseline evaluable participants determined to have Treatment-induced ADAs/Treatment-enhanced ADA during the study period. Treatment-induced ADA=negative or missing baseline ADA result(s) & at least one positive post-baseline ADA result. Treatment-enhanced ADA=a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. > baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs & treatment enhanced ADAs. Values have been rounded off to the nearest whole number. Safety population=all ITT participants from Cohort 1b (Phase Ib) who received at least one dose of study medication. 'Number Analysed'=number of participants with data available for analysis at the specified time point.

End point type

Primary

End point timeframe

Baseline up to approximately Month 24

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for Phase Ia cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint..
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Cohort 1b, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL
Number of subjects analysed	6	6
Units: percentage of participants
Baseline Prevalence of ADAs: Pola (n=6,6)	0	0
Post-Baseline ADAs: Pola (n=6,6)	0	0
Baseline Prevalence: ADAs to Obinutuzumab(n=6,5)	0	0
Post-Baseline ADA: Obinutuzumab (n=6,6)	0	0

No statistical analyses for this end point

Primary: Arms G+H: (Phase II NF Cohorts): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)

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End point title

Arms G+H: (Phase II NF Cohorts): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) ^[9]

End point description

Participants with positive results for ADA against pola at Baseline & any post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs/Treatment-enhanced ADAs during the study period. Treatment-induced ADA=negative or missing baseline ADA result(s)&at least one positive post-baseline ADA result. Treatment-enhanced ADA=a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u.>baseline titer result. Treatment emergent ADA=treatment-induced ADAs+treatment enhanced ADAs. Values are rounded off to nearest whole number.Safety population=ITT participants in Arms G&H who received at least one dose of study medication. 'Overall Number Analysed'=participants with data available for analysis. 'Number Analysed'=number of participants with data available for analysis at a specified timepoint.

End point type

Primary

End point timeframe

From Month 37 to Month 84 (up to approximately 47 months)

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for arms G and H, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL	Arm H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	41	62
Units: percentage of participants
number (not applicable)
Baseline Prevalence of ADAs: Pola (n=41,62)	0.0	1.6
Post-Baseline ADAs: Pola (n=39,60)	2.6	5.0

No statistical analyses for this end point

Primary: Phase II Randomised and NF Cohorts: Percentage of Participants with Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)

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End point title

Phase II Randomised and NF Cohorts: Percentage of Participants with Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) ^[10]

End point description

CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake≤mediastinum; 3=uptake>mediastinum but≤liver; 4=uptake moderately>liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1or after final dose of study treatment. Values have been rounded off to the nearest whole number. ITT population=all randomised participants in Phase II Randomised and NF cohorts irrespective of whether or not they received the study treatment.

End point type

Primary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for NF cohorts, hence no descriptive statistics were planned for other cohorts.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	106
Units: percentage of participants
number (confidence interval 95%)	69.2 (52.43 to 82.98)	63.4 (46.94 to 77.88)	42.5 (27.04 to 59.11)	17.5 (7.34 to 32.78)	39.6 (30.25 to 49.59)

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.5353

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

5.82

Confidence interval

level

95%

sides

2-sided

lower limit

-14.53

upper limit

25.38

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0128

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates (4.89

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.89

upper limit

42.63

Primary: Arm H (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

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End point title

Arm H (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC ^[11]

End point description

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Arm H (Phase II NF Cohort) irrespective of whether or not they received the study treatment.

End point type

Primary

End point timeframe

6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for arm H, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	64
Units: percentage of participants
number (confidence interval 95%)	42.2 (29.94 to 55.18)

No statistical analyses for this end point

Primary: Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized) ^[12]

End point description

Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms*day per millilitres. PK population included all ITT participants in Arm G (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Number Analysed' is the number of participants with data available for analysis at the specified time point. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint.

End point type

Primary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for arm G, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	32
Units: ng*day/mL
geometric mean (geometric coefficient of variation)
acMMAE (n=32)	2880 ( 0.15 )
Total Antibody (Ab) (n=0)	999999 ( 999999 )
MMAE (n=32)	21.6 ( 45 )

No statistical analyses for this end point

Primary: Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized) ^[13]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. PK evaluable population included all the ITT participants in Arm G (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. Here, 999999= participants were not analysed for this PK endpoint at the given timepoint. 'Number Analysed' is the number of participants with data available for analysis at the specified time point.

End point type

Primary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for arm G, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	32
Units: nanograms per millilitres (ng/mL)
geometric mean (geometric coefficient of variation)
acMMAE (n=32)	724 ( 10 )
Total Ab (n=0)	999999 ( 999999 )
MMAE (n=32)	2.01 ( 38 )

No statistical analyses for this end point

Primary: Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized) ^[14]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is millilitres per day per kilograms (mL/day/kg). As pre-specified in the protocol the analysis of this endpoint was based on sponsor's discretion however, sponsor opted to not collect data for this endpoint.

End point type

Primary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for arm G, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	0 ^[15]
Units: mL/day/kg
geometric mean (geometric coefficient of variation)	( )

Notes
[15] - Data was not collected for this endpoint per the sponsor's discretion.

No statistical analyses for this end point

Primary: Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized) ^[16]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. As pre-specified in the protocol the analysis of this endpoint was based on sponsor's discretion however, sponsor opted to not collect data for this endpoint.

End point type

Primary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was only for arm G, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	0 ^[17]
Units: millilitres per kilogram (mL/kg)
geometric mean (geometric coefficient of variation)	( )

Notes
[17] - Data was not collected for this endpoint per the sponsor's discretion.

No statistical analyses for this end point

Secondary: Phase II: Percentage of Participants with AEs

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End point title

Phase II: Percentage of Participants with AEs ^[18]

End point description

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. Safety population consisted of all ITT participants from Phase II who received at least one dose of study medication.

End point type

Secondary

End point timeframe

From the study start up to the end of the study (up to approximately 84 months)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	38	41	39	39	20	20	106
Units: percentage of participants
number (not applicable)	100	100	100	97.4	100	100	99.1

No statistical analyses for this end point

Secondary: Arms A and C (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin

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End point title

Arms A and C (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin ^[19]

End point description

Participants with positive results for ADA against pola at Baseline & any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points=post-baseline evaluable participants determined to have Treatment-induced ADAs/Treatment-enhanced ADA during the study period. Treatment-induced ADA=negative or missing baseline ADA result(s)&at least one positive post-baseline ADA result. Treatment-enhanced ADA=a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u.>baseline titer result. Treatment emergent ADA=treatment-induced ADAs+treatment enhanced ADAs.Values are rounded off to the nearest whole number. Safety population=ITT participants in Arms A&C who received at least one dose of study medication. 'Overall Number Analysed'=participants with data available for analysis. 'Number Analysed'=number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Baseline to approximately Month 24

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arms A and C, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL
Number of subjects analysed	38	36
Units: percentage of participants
number (not applicable)
Baseline Prevalence of ADAs (n=37,36)	0	0
Post-Baseline ADAs (n=38,35)	7.9	2.9

No statistical analyses for this end point

Secondary: Arms E and F (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

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End point title

Arms E and F (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab ^[20]

End point description

The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants with “Treatment-induced ADAs” or “Treatment-enhanced ADA” during study period. Treatment-induced ADA=negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA=participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA=of treatment-induced ADAs+treatment enhanced ADAs. Values have been rounded off to the nearest whole number. Safety population=ITT participants from Arm E and F (Phase II)who received at least one dose of study medication. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Baseline to approximately Month 24

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arms E and F, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	20	20
Units: percentage of participants
number (not applicable)
Baseline Prevalence of ADAs: Pola (n=19,18)	0	0
Post-Baseline ADAs: Pola (n=19,18)	5.3	5.6
Baseline Prevalence of ADAs: Obinutuzumab(n=20,20)	0	0
Post-Baseline ADAs: Obinutuzumab (n=19,18)	0	0

No statistical analyses for this end point

Secondary: Phase II: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator

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End point title

Phase II: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator ^[21]

End point description

CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow=normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Phase II irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	64.1 (47.18 to 78.80)	63.4 (46.94 to 77.88)	42.5 (27.04 to 59.11)	15.0 (5.71 to 29.84)	65.0 (40.78 to 84.61)	33.3 (14.59 to 56.97)	36.8 (27.63 to 46.71)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0061

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

27.5

Confidence interval

level

95%

sides

2-sided

lower limit

7.66

upper limit

44.74

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.8817

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-19.68

upper limit

20.86

Secondary: Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

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End point title

Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC ^[22]

End point description

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Phase II Expansion Cohorts and Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arm G, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	20	21	42
Units: percentage of participants
number (confidence interval 95%)	65.0 (40.78 to 84.61)	33.3 (14.59 to 56.97)	35.7 (21.55 to 51.97)

No statistical analyses for this end point

Secondary: Phase II: Percentage of Participants with Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator

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End point title

Phase II: Percentage of Participants with Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator ^[23]

End point description

OR at PRA=percentage of participants with CR/PR at PRA, assessed by investigator per MLRC. Per MLRC, CR per PET-CT=complete MR in lymph nodes(LN) and ELS with a score of 1, 2, or3 with/without residual mass on 5PS, i.e. 1=no uptake above background;2=uptake ≤ mediastinum;3=uptake mediastinum but ≤ liver;4=uptake moderately > liver;5=uptake markedly higher than liver and/or new lesions;no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR perPET-CT=partial MR in LN and ELS with a score of 4/5 with reduced uptake compared with baseline (B) and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with B (diffuse uptake compatible with reactive changes from chemotherapy allowed). ITT population=all randomised participants in Phase II irrespective of whether/not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	79.5 (63.54 to 90.70)	80.5 (63.13 to 91.18)	47.5 (31.51 to 63.87)	17.5 (7.34 to 32.78)	85.0 (62.11 to 96.79)	33.3 (14.59 to 56.97)	42.5 (32.91 to 52.43)

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.9523

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-18.66

upper limit

16.46

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0036

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.48

upper limit

47.37

Secondary: Phase II: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC

Top of page

End point title

Phase II: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC ^[24]

End point description

OR at PRA=percentage of participants with CR/PR at PRA, assessed by investigator per MLRC. Per MLRC, CR per PET-C=complete MR in LN and ELS with a score of 1, 2, or 3 with/without residual mass on 5PS, i.e.1=no uptake above background;2=uptake ≤ mediastinum;3=uptake mediastinum but ≤ liver;4=uptake moderately > liver;5=uptake markedly higher than liver and/or new lesions;no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR perPET-CT=partial MR in LN and ELS with a score of 4/5 with reduced uptake compared with baseline (B) and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with B (diffuse uptake compatible with reactive changes from chemotherapy allowed). ITT population=all randomised participants in Phase II irrespective of whether/not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	76.9 (60.67 to 88.87)	73.2 (57.06 to 85.78)	42.5 (27.04 to 59.11)	17.5 (7.34 to 32.78)	85.0 (62.11 to 96.79)	38.1 (18.11 to 61.56)	43.4 (33.80 to 53.37)

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.6574

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

3.75

Confidence interval

level

95%

sides

2-sided

lower limit

-15.14

upper limit

22.11

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0128

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.89

upper limit

42.63

Secondary: Phase II: Percentage of Participants with CR at PRA Based on CT only as Determined by Investigator

Top of page

End point title

Phase II: Percentage of Participants with CR at PRA Based on CT only as Determined by Investigator ^[25]

End point description

CR was determined by investigator at PRA per MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Phase II irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	46.2 (30.09 to 62.82)	19.5 (8.82 to 34.87)	20.0 (9.05 to 35.65)	5.0 (0.61 to 16.92)	20.0 (5.73 to 43.66)	14.3 (3.05 to 36.34)	14.2 (8.14 to 22.26)

No statistical analyses for this end point

Secondary: Phase II: Percentage of Participants with CR at PRA Based on CT Only as Determined by IRC

Top of page

End point title

Phase II: Percentage of Participants with CR at PRA Based on CT Only as Determined by IRC ^[26]

End point description

CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes (LN) and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). ITT population included all randomised participants in Phase II irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	20	106
Units: percentage of participants
number (confidence interval 95%)	41.0 (25.57 to 57.90)	36.6 (22.12 to 53.06)	22.5 (10.84 to 38.45)	2.5 (0.06 to 13.16)	50.0 (27.20 to 72.80)	23.8 (8.22 to 47.17)	17.9 (11.5 to 26.57)

No statistical analyses for this end point

Secondary: Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by Investigator

Top of page

End point title

Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by Investigator ^[27]

End point description

OR at PRA=percentage of participants with CR/PR at PRA, assessed by investigator per MLRC. Per MLRC, CR based on CT=complete radiologic response in LN & ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease, organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only=partial remission in LN and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable LN and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. As pre-specified in protocol data is reported combined for Arms G & H. ITT population=all randomised participants in Phase II irrespective of whether or not they received the study treatment. Values have been rounded off to the nearest whole number.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	79.5 (63.54 to 90.70)	75.6 (59.70 to 87.64)	45.0 (29.26 to 61.51)	15.0 (5.71 to 29.84)	80.0 (56.34 to 94.27)	33.3 (14.59 to 56.97)	42.5 (32.91 to 52.43)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0032

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.94

upper limit

47.12

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.6225

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

3.88

Confidence interval

level

95%

sides

2-sided

lower limit

-14.49

upper limit

21.72

Secondary: Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by IRC

Top of page

End point title

Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by IRC ^[28]

End point description

OR at PRA=percentage of participants with CR or PR at PRA, assessed by IRC per MLRC. Per MLRC, CR based on CT=complete radiologic response in LN & ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease, organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only=partial remission in LN and ELS with ≥ 50% decrease in SPD of up to 6 target measurable LN and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. Analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle=21 days=DLBCL cohorts & 28 days=FL cohorts). As pre-specified in the protocol data is reported combined for Arms G & H. ITT population=all randomised participants in Phase II irrespective of whether or not they received the study treatment. Values have been rounded off to the nearest whole number.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	74.4 (57.87 to 86.96)	80.5 (65.13 to 91.18)	40.0 (24.86 to 56.67)	15.0 (5.71 to 29.84)	80.0 (56.34 to 94.27)	38.1 (18.11 to 61.56)	41.5 (32.02 to 51.49)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0096

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.39

upper limit

42.33

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.4835

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

-6.13

Confidence interval

level

95%

sides

2-sided

lower limit

-24.14

upper limit

12.12

Secondary: Phase II: Percentage of Participants with Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator

Top of page

End point title

Phase II: Percentage of Participants with Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator ^[29]

End point description

BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=completeMR in LN & ELS, score=1, 2,3 with/without a residual mass on 5-PS;1=no uptake(UT) above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UTmarkedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology normal;if indeterminate,IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4 or 5, reduced UT than baseline (BL) & residual mass of any size;residual UT>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi &no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow=normal;if indeterminate,IHC negative.PR per CT=≥50% decrease in SPD of up to6 target nodes& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions. ITT population.

End point type

Secondary

End point timeframe

Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	39	41	40	40	20	21	106
Units: percentage of participants
number (confidence interval 95%)	89.7 (75.78 to 97.13)	90.2 (76.87 to 97.28)	70.0 (53.47 to 83.44)	32.5 (18.57 to 49.13)	90.0 (68.30 to 98.77)	52.4 (29.78 to 74.29)	62.3 (52.33 to 71.50)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0006

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

37.5

Confidence interval

level

95%

sides

2-sided

lower limit

15.64

upper limit

54.71

Arm A vs Arm B

Comparison groups

Arm A (Phase II Randomisation): Pola+BR in FL v Arm B (Phase II Randomisation): BR in FL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.939

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-15.07

upper limit

13.71

Secondary: DLBCL Cohorts: Percentage of Participants with BOR based PET-CT or CT Only as Determined by IRC

Top of page

End point title

DLBCL Cohorts: Percentage of Participants with BOR based PET-CT or CT Only as Determined by IRC ^[30]

End point description

BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in LN & ELS, score=1, 2,3 with/without residual mass on 5-PS;1=no UT above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver &/or new lesions; no evidence of FDG-avid disease, bone marrow morphology normal; if indeterminate, IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4/5, reduced UT than BL &residual mass of any size; residual UT>UT in normal marrow but reduced thanBL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion; organ enlargement regressed to normal; no new lesions; bone marrow=normal; if indeterminate, IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by≥50% in length beyond normal, no new lesions. ITT population.

End point type

Secondary

End point timeframe

Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for DLBCL cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	40	40	21	106
Units: percentage of participants
number (confidence interval 95%)	62.5 (45.80 to 77.27)	25.0 (12.69 to 41.20)	42.9 (21.82 to 65.98)	57.5 (47.57 to 67.09)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0005

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rates

Point estimate

37.5

Confidence interval

level

95%

sides

2-sided

lower limit

15.82

upper limit

54.62

Secondary: DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator

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End point title

DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator ^[31]

End point description

DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL&residual mass of any size at interim for LN & ELS;residual UT>UT in normal bone marrow but<than BL.CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN&extranodal sites, absent/normal/regressed but no<in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions. ITT population.

End point type

Secondary

End point timeframe

From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for DLBCL cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	28	13	11	66
Units: months
median (confidence interval 95%)	12.665 (5.782 to 27.926)	4.074 (2.563 to 12.682)	16.099 (2.825 to 27.860)	11.335 (6.242 to 16.197)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0245

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.91

Secondary: DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC

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End point title

DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC ^[32]

End point description

End point type

Secondary

End point timeframe

From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for DLBCL cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	25	10	9	61
Units: months
median (confidence interval 95%)	10.908 (5.684 to 40.674)	10.645 (3.975 to 19.647)	25.758 (9.692 to 46.752)	13.437 (8.641 to 20.041)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.2451

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

1.43

Secondary: DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator

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End point title

DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator ^[33]

End point description

PFS was defined as the time randomisation or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data is reported combined for Arms G and H. ITT population included all randomised participants in DLBCL cohorts irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for DLBCL cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	40	40	21	106
Units: months
median (confidence interval 95%)	7.491 (4.928 to 16.953)	2.037 (1.544 to 3.713)	5.125 (2.103 to 18.234)	5.881 (4.764 to 7.524)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.56

Secondary: DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC

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End point title

DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC ^[34]

End point description

PFS was defined as the time randomisation or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data is reported combined for Arms G and H. ITT population included all randomised participants in DLBCL cohorts irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

From the date of randomisation or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for DLBCL cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	40	40	21	106
Units: months
median (confidence interval 95%)	9.248 (6.045 to 13.930)	3.713 (2.070 to 4.534)	5.848 (2.103 to 11.893)	6.965 (5.092 to 9.823)

Arm C vs Arm D

Comparison groups

Arm C (Phase II Randomisation): Pola+BR in DLBCL v Arm D (Phase II Randomisation): BR in DLBCL

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0003

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

0.66

Secondary: Phase II NF Cohort: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator

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End point title

Phase II NF Cohort: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator ^[35]

End point description

CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. As pre-specified in the protocol data is reported combined for Arms G and H. ITT population included all randomised participants in Phase II NF cohort irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21) or last dose of study drug (up to approximately 23 weeks)

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II NF cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: percentage of participants
number (confidence interval 95%)	36.8 (27.63 to 46.71)

No statistical analyses for this end point

Secondary: Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by Investigator

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End point title

Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by Investigator ^[36]

End point description

OR at PRA=percentage of participants with CR/PR at PRA, assessed by investigator per MLRC. Per MLRC, CR per PET-CT=complete MR in LN & ELS with a score of 1, 2, or 3 with/without residual mass on 5PS, i.e., 1=no uptake above background;2=uptake ≤ mediastinum;3=uptake mediastinum but ≤ liver;4=uptake moderately > liver;5=uptake markedly higher than liver &/or new lesions; no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR per PET-CT=partial MR in LN and ELS with a score of 4/5 with reduced uptake compared with baseline (BL) & residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with BL (diffuse uptake compatible with reactive changes from chemotherapy allowed). ITT population=all randomised participants in Phase II NF cohort irrespective of whether/not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G & H.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for NF cohorts, hence no descriptive statistics were planned for other cohorts.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: percentage of participants
number (confidence interval 95%)	42.5 (32.91 to 52.43)

No statistical analyses for this end point

Secondary: Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC

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End point title

Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC ^[37]

End point description

OR at PRA=percentage of participants with CR/PR at PRA, per the IRC per MLRC. Per MLRC, CR per PET-CT complete MR in LN & ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where1=no uptake above background;2=uptake ≤ mediastinum;3=uptake mediastinum but≤ liver;4=uptake moderately> liver;5=uptake markedly<than liver &/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow, normal morphology; if indeterminate, IHC negative.PR per PET-CT=partial MR in LN and ELS with a score of 4/5 with reduced UT compared with BL & residual mass(es) of any size at interim, residual UT higher than UT in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).As pre-specified in the protocol data is reported combined for Arms G and H. ITT population=all randomised participants in NF cohort irrespective of whether they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for NF cohorts, hence no descriptive statistics were planned for other cohorts.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: percentage of participants
number (confidence interval 95%)	43.4 (33.80 to 53.37)

No statistical analyses for this end point

Secondary: Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the IRC

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End point title

Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the IRC ^[38]

End point description

BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN &ELS, score=1, 2,3 with/without a residual mass on 5-PS;1=no UT above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver &/or new lesions; no evidence of FDG-avid disease, bone marrow morphology normal; if indeterminate, IHC negative.PR per PET-CT=partial MR in LN &ELS, score=4 or 5, reduced UT than BL & residual mass of any size; residual UT>UT in normal marrow but reduced than BL. CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion; organ enlargement regressed to normal; no new lesions; bone marrow=normal; if indeterminate, IHC negative.PR per CT=≥50% decrease in SPD of up to6 target nodes& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions. ITT population.

End point type

Secondary

End point timeframe

Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: percentage of participants
number (confidence interval 95%)	57.5 (47.57 to 67.09)

No statistical analyses for this end point

Secondary: Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the Investigator

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End point title

Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the Investigator ^[39]

End point description

BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in LN & ELS, score=1, 2,3 with/without residual mass on 5-PS;1=no UT above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver &/or new lesions; no evidence of FDG-avid disease, bone marrow morphology normal; if indeterminate, IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4/5, reduced UT than BL & residual mass of any size; residual UT>UT in normal marrow but reduced thanBL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion; organ enlargement regressed to normal; no new lesions; bone marrow=normal; if indeterminate, IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by≥50% in length beyond normal, no new lesions. ITT population.

End point type

Secondary

End point timeframe

UpUp to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II NF cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: percentage of participants
number (confidence interval 95%)	62.3 (52.33 to 71.50)

No statistical analyses for this end point

Secondary: Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator

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End point title

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator ^[40]

End point description

PFS was defined as the time from randomisation or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data is reported combined for Arms G and H. ITT population included all randomised participants in Phase II NF cohort irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

From the date of randomisation or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: months
median (confidence interval 95%)	5.881 (4.764 to 7.524)

No statistical analyses for this end point

Secondary: Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

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End point title

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

End point description

DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL&residual mass of any size at interim for LN & ELS;residual UT>UT in normal bone marrow but<than BL.CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN&extranodal sites, absent/normal/regressed but no<in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions. ITT population.

End point type

Secondary

End point timeframe

From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	61
Units: months
median (confidence interval 95%)	13.437 (8.641 to 20.041)

No statistical analyses for this end point

Secondary: Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator

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End point title

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator

End point description

End point type

Secondary

End point timeframe

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	66
Units: months
median (confidence interval 95%)	11.335 (6.242 to 16.197)

No statistical analyses for this end point

Secondary: Phase II NF Cohorts: Overall Survival (OS)

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End point title

Phase II NF Cohorts: Overall Survival (OS) ^[41]

End point description

OS was defined as the time from the date of randomisation or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H. ITT population included all participants in Phase II NF cohort who were randomised, whether or not the participants received the assigned treatment.

End point type

Secondary

End point timeframe

From Month 37 to Month 84 (Up to approximately 47 months)

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II NF cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: months
median (confidence interval 95%)	12.320 (8.279 to 16.986)

No statistical analyses for this end point

Secondary: Phase II NF Cohorts: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator

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End point title

Phase II NF Cohorts: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator ^[42]

End point description

EFS was defined as time from randomisation to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data is reported combined for Arms G and H. ITT population included all randomised participants in Phase II NF cohort irrespective of whether or not they received the study treatment. 'Overall Number Analysed' are the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

From Month 37 to Month 84 (Up to approximately 47 months)

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II NF cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: months
median (confidence interval 95%)	5.092 (4.402 to 6.867)

No statistical analyses for this end point

Secondary: Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC

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End point title

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC ^[43]

End point description

PFS was defined as the time from randomisation or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data is reported combined for Arms G and H. ITT population included all randomised participants in NF cohort irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

From the date of randomisation or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 47 months)

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	106
Units: months
median (confidence interval 95%)	6.965 (5.092 to 9.823)

No statistical analyses for this end point

Secondary: Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

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End point title

Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

End point description

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol Arms G and H have been combined to provide a more precise 95% CI. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	42
Units: percentage of participants
number (confidence interval 95%)	35.7 (21.55 to 51.97)

No statistical analyses for this end point

Secondary: Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on CT only as Determined by Investigator

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End point title

Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on CT only as Determined by Investigator

End point description

CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	42
Units: percentage of participants
number (confidence interval 95%)	9.5 (2.66 to 22.62)

No statistical analyses for this end point

Secondary: Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on CT only as Determined by IRC

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End point title

Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on CT only as Determined by IRC

End point description

CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number. ITT population included all randomised participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	42
Units: percentage of participants
number (confidence interval 95%)	14.3 (5.43 to 28.54)

No statistical analyses for this end point

Secondary: Arm G (Phase II NF Cohort): Percentage of Participants with OR at PRA Based on CT only as Determined by Investigator

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End point title

Arm G (Phase II NF Cohort): Percentage of Participants with OR at PRA Based on CT only as Determined by Investigator

End point description

OR at PRA=percentage of participants with CR/PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT=complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only = partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. ITT population included all randomised participants in Arm G irrespective of whether or not they received the study treatment. Values have been rounded off to the nearest whole number. The analysis was done 6-8 weeks after Cycle 6 Day 1 (each cycle=21 days for DLBCL cohorts).

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	42
Units: percentage of participants
number (confidence interval 95%)	38.1 (23.57 to 54.36)

No statistical analyses for this end point

Secondary: Arm G (Phase II NF Cohort): Percentage of Participants with OR at PRA Based on CT only as Determined by IRC

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End point title

Arm G (Phase II NF Cohort): Percentage of Participants with OR at PRA Based on CT only as Determined by IRC

End point description

OR at PRA=percentage of participants with CR or PR at the PRA, as assessed by the IRC perMLRC. Per MLRC, CR based on CT =complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only = partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. ITT population included all randomised participants in Arm G irrespective of whether or not they received the study treatment. Values have been rounded off to the nearest whole number. The analysis was done 6-8 weeks after Cycle 6 Day 1 (each cycle=21 days for DLBCL cohorts).

End point type

Secondary

End point timeframe

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	42
Units: percentage of participants
number (confidence interval 95%)	33.3 (19.57 to 49.55)

No statistical analyses for this end point

Secondary: Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

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End point title

Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE ^[44]

End point description

PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. Here, 9999= data is not evaluable as the samples were below lower limit of quantification (BLLQ); 99999= Since only 1 participant was analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants Phase Ib and Phase II who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoint. Cycle=C, Day = D, Post dose= Pd.

End point type

Secondary

End point timeframe

Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No descriptive statistics were planned for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	6	6	6	6	36	36	18	19
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1 D2: Pre-dose (n=6,6,6,36,36,17,16)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D2: 30 min Pd (n=6,6,6,36,35,18,19)	654 ( 29.3 )	617 ( 26.2 )	719 ( 26.7 )	718 ( 14.2 )	492 ( 241.6 )	643 ( 24.7 )	453 ( 682.8 )	472 ( 617.2 )
C1 D8 (n=5,6,6,6,0,0,0,0)	29.4 ( 5887.2 )	75.9 ( 40.8 )	90.7 ( 46.1 )	109 ( 48.2 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C1 D15 (n=5,6,5,6,0,0,0,0)	12.2 ( 1626.9 )	25.4 ( 29.8 )	28.9 ( 48.6 )	34.4 ( 37.3 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C2 D1: Pre-dose (n=6,6,6,35,33,18,16)	3.21 ( 546.5 )	12.4 ( 47.9 )	8.75 ( 77.7 )	16.6 ( 25.6 )	4.72 ( 159.8 )	12.7 ( 120.5 )	9.05 ( 74.4 )	13.1 ( 45.2 )
C2 D1: 30 min Pd (n=6,6,6,6,0,0,0,0)	685 ( 22.0 )	683 ( 20.1 )	803 ( 20.1 )	834 ( 13.5 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C4 D1: Pre-dose (n=5,3,6,4,31,23,16,12)	12.2 ( 26.1 )	21.1 ( 46.7 )	15.3 ( 61.9 )	26.2 ( 22.1 )	11.2 ( 109.3 )	20.7 ( 46.4 )	15.2 ( 30.5 )	19.6 ( 30.5 )
C4 D1: 30 min Pd (n=5,3,6,4,29,23,17,12)	748 ( 23.4 )	754 ( 14.4 )	734 ( 22.0 )	716 ( 13.7 )	689 ( 20.9 )	645 ( 21.4 )	829 ( 20.3 )	709 ( 10.1 )
Unscheduled Visit (n=0,0,0,0,0,3,2,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	41.1 ( 49.4 )	53.0 ( 58.0 )	999999 ( 999999 )
Unscheduled Visit: Pre-dose (n=0,0,0,0,1,1,0,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	1.21 ( 99999 )	0.180 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )
Unscheduled Visit:30min Pd(n=0,0,0,0,0,1,0,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	915 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )
Study Treatment Completion (n=0,0,1,0,28,27,14,8)	999999 ( 999999 )	999999 ( 999999 )	18.7 ( 99999 )	999999 ( 999999 )	10.7 ( 181.7 )	14.2 ( 95.7 )	14.9 ( 69.4 )	12.3 ( 109.4 )

No statistical analyses for this end point

Secondary: Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: acMMAE

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End point title

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: acMMAE

End point description

PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. PK evaluable population included all the ITT participants in Arm G+H (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	102
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 2: Post Dose (n=102)	653 ( 237 )
Cycle 2 Day 1: Pre-dose (n=94)	14.6 ( 8.66 )
Cycle 2 Day 1: Post Dose (n=92)	667 ( 155 )
Cycle 4 Day 1: Pre-dose (n=61)	23.2 ( 8.59 )
Cycle 4 Day 1: Post Dose (n=60)	659 ( 156 )

No statistical analyses for this end point

Secondary: Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab

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End point title

Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab ^[45]

End point description

PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since only 1 participant was analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants who received at least one study treatment and who provided suitable PK samples. Overall Number Analysed are the number of participants with data available for analysis. 'Number Analysed is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No descriptive statistics were planned for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	6	6	6	6	36	36	18	19
Units: grams per milliliters (g/mL)
geometric mean (geometric coefficient of variation)
C1 D2: Pre-dose (n=6,6,6,6,36,36,17,18)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D2: 30 min Pd (n=6,6,6,6,36,35,18,19)	33.2 ( 28.4 )	36.6 ( 25.4 )	37.5 ( 29.1 )	34.3 ( 20.3 )	35.4 ( 27.7 )	34.6 ( 26.2 )	32.4 ( 22.8 )	38.3 ( 20.3 )
C1 D8 (n=5,6,66,0,0,0,0)	3.43 ( 4393.4 )	9.01 ( 43.7 )	10.2 ( 39.3 )	10.0 ( 31.9 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C1 D15 (n=5,6,66,0,0,0,0)	1.83 ( 1784.3 )	4.26 ( 35.3 )	4.61 ( 40.6 )	5.22 ( 28.4 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C2 D1: Pre-dose (n=6, 6,6,36,33,18,16)	0.696 ( 941.2 )	2.31 ( 54.2 )	2.20 ( 76.1 )	3.70 ( 27.4 )	1.23 ( 203.1 )	2.48 ( 137.6 )	2.20 ( 100.6 )	2.83 ( 41.8 )
C2 D1: 30 min Pd (n=6,6,6,6,0,0,0,0)	35.8 ( 25.9 )	39.5 ( 28.3 )	43.4 ( 31.1 )	42.2 ( 22.9 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C4 D1: Pre-dose (n=5,3,6,4,32,23,16,12)	3.44 ( 30.5 )	5.03 ( 59.0 )	4.61 ( 62.2 )	6.26 ( 18.3 )	3.61 ( 97.8 )	5.72 ( 39.9 )	4.82 ( 20.8 )	5.03 ( 29.3 )
C4 D1: 30 min Pd (n=5,3,6,4,31,23,17,12)	40.2 ( 27.2 )	44.6 ( 11.0 )	43.0 ( 25.8 )	47.1 ( 24.2 )	44.8 ( 24.3 )	40.6 ( 20.6 )	55.0 ( 21.3 )	37.5 ( 11.6 )
Follow up on Month 3, Day 1 (n=5,3,5,2,23,18,15,8)	0.164 ( 51.9 )	0.771 ( 193.4 )	0.910 ( 82.8 )	0.394 ( 27.1 )	0.265 ( 209.9 )	0.316 ( 266.2 )	0.489 ( 174.2 )	0.543 ( 126.7 )
Follow up on Month 6, Day 1 (n=5,3,5,2,21,12,10,7)	0.0250 ( 0.0 )	0.0788 ( 230.0 )	0.219 ( 96.6 )	0.104 ( 18.5 )	0.0539 ( 145.7 )	0.0564 ( 195.7 )	0.0920 ( 123.5 )	0.150 ( 206.6 )
Follow up on Month 12, Day 1 (n=4,3,4,3,13,9,6,3)	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0298 ( 35.9 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0301 ( 60.6 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )
Follow up on Month 18, Day 1 (n=2,3,2,2,2,3, 3,3)	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 0.0 )
Follow up on Month 24, Day 1 (n=2,3,1,1,0,0,0,1)	0.0250 ( 0.0 )	0.0250 ( 0.0 )	0.0250 ( 99999 )	0.0250 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.0250 ( 99999 )
Unscheduled Visit (n=3,2,0,1,0,4,3,0)	0.0250 ( 0.0 )	0.0250 ( 0.0 )	999999 ( 999999 )	0.0250 ( 99999 )	999999 ( 999999 )	1.65 ( 5419.8 )	1.23 ( 30267.8 )	999999 ( 999999 )
Unscheduled Visit: Pre-dose (n=0,0,0,0,1,1,0,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.279 ( 99999 )	0.0250 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )
Unscheduled Visit: 30 min Pd (n=0,0,0,0,0,1,0,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	42.0 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )
Treatment Completion Visit (n=0,0,1,0,27,27,14,8)	999999 ( 999999 )	999999 ( 999999 )	5.34 ( 999999 )	999999 ( 999999 )	3.34 ( 180.5 )	4.33 ( 69.4 )	4.57 ( 57.2 )	3.23 ( 79.3 )

No statistical analyses for this end point

Secondary: Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab

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End point title

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab

End point description

PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. PK evaluable population included all the ITT participants in Arm G+H (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. Overall Number Analysed are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	103
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 2: Post Dose (n=103)	33.9 ( 11.7 )
Cycle 2 Day 1: Pre-dose (n=94)	3.27 ( 4.37 )
Cycle 2 Day 1: Post Dose (n=92)	36.0 ( 8.71 )
Cycle 4 Day 1: Pre-dose (n=63)	5.41 ( 1.79 )
Cycle 4 Day 1: Post Dose (n=61)	39.2 ( 7.30 )

No statistical analyses for this end point

Secondary: Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

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End point title

Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE ^[46]

End point description

PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since only 1 participant was analyzed, the geometric coefficient of variation was not calculated; 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants Phase Ib and Phase II who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Notes
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No descriptive statistics were planned for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	6	6	6	6	36	36	18	18
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1 D2: Pre-dose (n=6,6,6,6,35,36,17,17)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D2: 30 min Pd (n=6,6,6,6,36,3,18,18)	0.726 ( 297.5 )	0.234 ( 80.2 )	0.397 ( 67.7 )	0.327 ( 41.4 )	0.402 ( 80.2 )	0.315 ( 105.3 )	0.243 ( 101.8 )	0.456 ( 103.1 )
C1 D8 (n=5,6,6,6,0,0,0,0)	1.48 ( 100.8 )	1.84 ( 78.4 )	1.96 ( 51.5 )	2.34 ( 21.4 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C1 D15 (n=5,6,5,6,0,0,0,0)	0.311 ( 93.8 )	0.531 ( 88.5 )	0.705 ( 60.0 )	0.688 ( 19.5 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C2 D1: Pre-dose (n=6,6,6,6,35,33,17,15)	0.0264 ( 70.8 )	0.158 ( 79.4 )	0.0512 ( 129.3 )	0.150 ( 44.4 )	0.0373 ( 81.5 )	0.159 ( 80.9 )	0.0451 ( 76.9 )	0.186 ( 86.8 )
C2 D1: 30 min Pd (n=6,6,6,6,0,0,0,0)	0.185 ( 54.2 )	0.263 ( 72.7 )	0.231 ( 53.5 )	0.345 ( 31.9 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
C4 D1: Pre-dose (n=5,3,6,4,32,23,15,12)	0.0414 ( 102.9 )	0.133 ( 72.6 )	0.0511 ( 68.3 )	0.150 ( 44.3 )	0.0554 ( 77.3 )	0.158 ( 58.2 )	0.0481 ( 83.2 )	0.141 ( 102.3 )
C4 D1: 30 min Pd (n=4,3,6,4,29,23,15,12)	0.234 ( 35.0 )	0.266 ( 27.0 )	0.167 ( 39.2 )	0.257 ( 32.3 )	0.198 ( 32.0 )	0.316 ( 38.9 )	0.195 ( 38.1 )	0.283 ( 56.9 )
Unscheduled Visit (n=0,0,0,0,0,0,2,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.738 ( 64.6 )	999999 ( 999999 )
Unscheduled Visit: Pre-dose (n=0,0,0,0,1,1,0,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.0180 ( 99999 )	0.0180 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )
Unscheduled Visit: 30 min Pd (n=0,0,0,0,1,01,0,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.114 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )
Treatment Completion (n=0,0,1,0,28,27,13,8)	999999 ( 999999 )	999999 ( 999999 )	0.0595 ( 99999 )	999999 ( 999999 )	0.0506 ( 113.0 )	0.0749 ( 165.9 )	0.0682 ( 110.4 )	0.150 ( 179.4 )

No statistical analyses for this end point

Secondary: Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

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End point title

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

End point description

PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. PK evaluable population included all the ITT participants in Arm G+H (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose

End point values	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	103
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 2: Post Dose (n=103)	0.590 ( 1.08 )
Cycle 2 Day 1: Pre-dose (n=94)	0.229 ( 0.248 )
Cycle 2 Day 1: Post Dose (n=91)	0.316 ( 0.213 )
Cycle 4 Day 1: Pre-dose (n=61)	0.186 ( 0.118 )
Cycle 4 Day 1: Post Dose (n=60)	0.256 ( 0.118 )

No statistical analyses for this end point

Secondary: Plasma Concentration of Bendamustine

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End point title

Plasma Concentration of Bendamustine ^[47]

End point description

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H). Here, 9999= data is not evaluable as the samples were BLLQ. PK evaluable population included all the ITT participants who Phase Ib and Phase II received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No descriptive statistics were planned for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	0 ^[48]	0 ^[49]	0 ^[50]	0 ^[51]	37	39	35	33	18	19
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1 D2: Pre-dose (n=0,0,0,0,37,39,34,33,18,19)	( )	( )	( )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D2: 5 min Pd (n=0,0,0,0,35,38,35,31,18,19)	( )	( )	( )	( )	2130 ( 665.6 )	2810 ( 222.7 )	2740 ( 550.9 )	1700 ( 1865.5 )	3090 ( 68.3 )	3790 ( 119.4 )
C1 D2: 1h Pd (n=0,0,0,0,35,39,34,31,17,18)	( )	( )	( )	( )	456 ( 167.8 )	353 ( 187.9 )	518 ( 154.2 )	451 ( 380.2 )	478 ( 111.4 )	639 ( 165.6 )
C1 D2: 2h Pd (n=0,0,0,0,34,39,34,333,17,16)	( )	( )	( )	( )	84.4 ( 173.5 )	55.1 ( 236.5 )	93.8 ( 250.5 )	101 ( 375.8 )	62.8 ( 104.3 )	128 ( 196.7 )
C1 D2: 3h Pd (n=0,0,0,0,33,38,34,332,17,15)	( )	( )	( )	( )	20.5 ( 220.1 )	12.7 ( 246.4 )	23.5 ( 461.0 )	21.5 ( 509.9 )	12.4 ( 132.0 )	28.2 ( 287.4 )
C1 D2: 4h Pd (n=0,0,0,0,31,37,31,333,17,15)	( )	( )	( )	( )	7.60 ( 278.5 )	4.58 ( 268.4 )	8.11 ( 724.8 )	8.08 ( 615.9 )	3.30 ( 147.2 )	6.18 ( 131.0 )

Notes
[48] - Participants were not analysed for this PK endpoint.
[49] - Participants were not analysed for this PK endpoint.
[50] - Participants were not analysed for this PK endpoint.
[51] - Participants were not analysed for this PK endpoint.

No statistical analyses for this end point

Secondary: Serum Concentration of Rituximab

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End point title

Serum Concentration of Rituximab ^[52]

End point description

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H). Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since only 1 participant was analyzed, the geometric coefficient of variation was not calculated; 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) and Arms A-D (Phase II) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No descriptive statistics were planned for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL
Number of subjects analysed	0 ^[53]	0 ^[54]	37	38	34	34
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1 D1: Pre-dose (n=0,0,37,38,34,34)	( )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D1: 30 min Pd (n=0,0,32,38,34,33)	( )	( )	182 ( 27.2 )	202 ( 24.5 )	188 ( 19.9 )	180 ( 18.0 )
C2 D1: Pre-dose (n=0,0,36,33,29,27)	( )	( )	22.8 ( 79.2 )	20.2 ( 145.9 )	34.9 ( 89.9 )	34.6 ( 69.7 )
C 4 D1: Pre-dose (n=0,0,31,33,21,14)	( )	( )	65.1 ( 46.5 )	62.3 ( 42.7 )	74.7 ( 50.9 )	83.3 ( 49.1 )
Unscheduled: Pre-dose (n=0,0,2,0,1,1)	( )	( )	30.6 ( 118.0 )	999999 ( 999999 )	298 ( 99999 )	2.00 ( 99999 )
Unscheduled: 30 min Pd (n=0,0,0,0,0,1)	( )	( )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	165 ( 99999 )

Notes
[53] - Participants were not analysed for this PK endpoint.
[54] - Participants were not analysed for this PK endpoint.

No statistical analyses for this end point

Secondary: Serum Concentration of Obinutuzumab

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End point title

Serum Concentration of Obinutuzumab ^[55]

End point description

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since only 1 participant was analysed, the geometric coefficient of variation was not calculated; 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1b (Phase 1b) and Arms E and F (Phase II) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No descriptive statistics were planned for this endpoint.

End point values	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	6	6	19	19
Units: g/mL
geometric mean (geometric coefficient of variation)
C1 D1: Pre-dose (6,5,19,19)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D1: 30 min Pd (n=0,0,14,13)	999999 ( 999999 )	999999 ( 999999 )	341 ( 22.1 )	221 ( 105.5 )
C2 D1: Pre-dose (n=6,6,18,17)	283 ( 38.4 )	412 ( 40.8 )	301 ( 39.3 )	349 ( 58.0 )
C4 D1: Pre-dose (n=6,4,17,12)	293 ( 53.8 )	359 ( 28.9 )	291 ( 37.9 )	290 ( 36.4 )
C4 D1: 30 min Pd (n=0,0,16,12)	999999 ( 999999 )	999999 ( 999999 )	701 ( 27.4 )	642 ( 29.5 )
Follow up on Month 3, D1 (n=5,2,16,8)	67.7 ( 47.8 )	28.8 ( 17.0 )	38.5 ( 167.8 )	55.1 ( 119.9 )
Follow up on Month 6, D1 (n=5,2,10,7)	11.5 ( 56.6 )	5.38 ( 12.4 )	7.64 ( 412.2 )	15.8 ( 137.6 )
Follow up on Month 12, D1 (n=4,3,6,2)	0.237 ( 717.6 )	0.389 ( 119.3 )	0.162 ( 569.7 )	0.732 ( 18.7 )
Follow up on Month 18, D1 (n=2,2,7,3)	0.00978 ( 1188.5 )	0.0107 ( 170.5 )	0.00842 ( 347.4 )	0.0460 ( 86.9 )
Follow up on Month 24, D1 (n=1,1,0,1)	0.00203 ( 99999 )	0.00203 ( 99999 )	99999 ( 99999 )	0.00203 ( 99999 )
Unscheduled (n=0,1,1,0)	999999 ( 999999 )	3.09 ( 99999 )	20.8 ( 999999 )	999999 ( 999999 )
Unscheduled Visit: Pre-dose (n=0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	99999 ( 99999 )	0.0626 ( 99999 )
Unscheduled Visit: 30 min Pd (n=0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	99999 ( 99999 )	349 ( 99999 )
Treatment Completion Visit (n=1,0,14,8)	367 ( 99999 )	999999 ( 999999 )	242 ( 52.7 )	232 ( 46.2 )

No statistical analyses for this end point

Secondary: Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

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End point title

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a ^[56]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Cmax was not evaluated for Bendamustine and Rituximab.

End point type

Secondary

End point timeframe

Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL
Number of subjects analysed	6	6
Units: ng/mL
arithmetic mean (standard deviation)
acMMAE: Cycle 1 (n=6,6)	676 ( 176 )	634 ( 158 )
acMMAE: Cycle 2 (n=6,6)	697 ( 129 )	694 ( 138 )
acMMAE: Cycle 4 (n=5,3)	763 ( 159 )	759 ( 107 )
Total Ab: Cycle 1 (n=6,6)	34.3 ( 8.57 )	37.6 ( 9.42 )
Total Ab: Cycle 2 (n=6,6)	36.6 ( 8.00 )	40.6 ( 9.46 )
Total Ab: Cycle 4 (n=5,3)	41.3 ( 9.98 )	44.8 ( 5.06 )
Unconjugated MMAE: Cycle 1 (n=6,6)	3.31 ( 4.00 )	2.21 ( 1.34 )
Unconjugated MMAE: Cycle 2 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 1 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 2 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 1(n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 2 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

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End point title

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b ^[57]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Cmax was not evaluated for Bendamustine and Obinutuzumab.

End point type

Secondary

End point timeframe

Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL
Number of subjects analysed	6	6
Units: ng/mL
arithmetic mean (standard deviation)
acMMAE: Cycle 1 (n=6,6)	738 ( 165 )	725 ( 104 )
acMMAE: Cycle 2 (n=6,6)	816 ( 168 )	841 ( 115 )
acMMAE: Cycle 4 (n=6,4)	749 ( 158 )	721 ( 97.7 )
Total Ab: Cycle 1 (n=6,6)	38.7 ( 9.84 )	34.9 ( 7.52 )
Total Ab: Cycle 2 (n=6,6)	45.0 ( 12.1 )	43.1 ( 9.52 )
Total Ab: Cycle 4 (n=6,4)	44.2 ( 11.2 )	48.2 ( 12.5 )
Unconjugated MMAE: Cycle 1 (n=6,6)	2.17 ( 1.08 )	2.39 ( 0.492 )
Unconjugated MMAE: Cycle 2 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 1 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 2(n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 1 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 2 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

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End point title

Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C ^[58]

End point description

PK of three pola analytes: acMMAE, total antibody and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms A and C who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints.

End point type

Secondary

End point timeframe

Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL
Number of subjects analysed	36	35
Units: ng/mL
arithmetic mean (standard deviation)
acMMAE: Cycle 1 (n=36,35)	622 ( 194 )	661 ( 149 )
acMMAE: Cycle 4 (n=29,23)	703 ( 150 )	659 ( 135 )
Total Ab: Cycle 1 (n=36,35)	36.7 ( 9.54 )	35.7 ( 8.50 )
Total Ab: Cycle 4 (n=31,23)	46.1 ( 11.4 )	41.4 ( 8.29 )
Unconjugated MMAE: Cycle 1 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 1 (n=34,33)	3.57 ( 2.06 )	4.23 ( 2.26 )
Bendamustine: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab: Cycle 1 (n=32,34)	188 ( 49.2 )	191 ( 35.9 )
Rituximab: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: Cmax of Bendamustine and Rituximab in Arms B and D

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End point title

Phase II: Cmax of Bendamustine and Rituximab in Arms B and D ^[59]

End point description

PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm B (Phase II Randomisation): BR in FL	Arm D (Phase II Randomisation): BR in DLBCL
Number of subjects analysed	38	33
Units: ug/mL
arithmetic mean (standard deviation)
Bendamustine (n=34,30)	3.21 ( 2.09 )	3.85 ( 2.91 )
Rituximab (n=33,34)	207 ( 50.1 )	183 ( 33.6 )

No statistical analyses for this end point

Secondary: Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F

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End point title

Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F ^[60]

End point description

PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. Overall Number Analysed are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints.

End point type

Secondary

End point timeframe

Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	18	19
Units: ug/mL
arithmetic mean (standard deviation)
acMMAE: Cycle 1 (n=18,19)	692 ( 230 )	703 ( 211 )
acMMAE: Cycle 4 (n=17,12)	845 ( 165 )	713 ( 70.6 )
Total Ab: Cycle 1 (n=18,19)	33.3 ( 8.04 )	39.0 ( 7.63 )
Total Ab: Cycle 4 (n=17,12)	56.1 ( 11.2 )	37.8 ( 4.51 )
Unconjugated MMAE: Cycle 1 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine: Cycle 1 (n=16,19)	3.30 ( 1.58 )	5.47 ( 4.30 )
Bendamustine: Cycle 4 (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Obinutuzumab: Cycle 1 (n=14,13)	349 ( 72.8 )	274 ( 118 )
Obinutuzumab: Cycle 4 (n=16,12)	727 ( 217 )	666 ( 190 )

No statistical analyses for this end point

Secondary: Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)

End point description

End point type

Secondary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	0 ^[61]
Units: nanograms per milliliters (ng/mL)
geometric mean (geometric coefficient of variation)	( )

Notes
[61] - Data was not collected for this endpoint per the sponsor's discretion.

No statistical analyses for this end point

Secondary: Phase Ib: AUC from Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

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End point title

Phase Ib: AUC from Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a ^[62]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day*micrograms per millilitres (day*ug/mL]). Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Overall number analysed' is the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for bendamustine and rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL
Number of subjects analysed	4	6
Units: day*ug/mL
geometric mean (geometric coefficient of variation)
acMMAE (n=4,6)	2830 ( 12.1 )	2110 ( 28.4 )
Total Ab (n=4,6)	298 ( 4.9 )	214 ( 35.9 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

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End point title

Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b ^[63]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for bendamustine and obinutuzumab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL
Number of subjects analysed	6	6
Units: day*ug/mL
geometric mean (geometric coefficient of variation)
acMMAE (n=5,6)	2600 ( 34.4 )	2650 ( 16.4 )
Total Ab (n=6,6)	267 ( 30.2 )	252 ( 21.6 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Obinutuzumab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

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End point title

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C ^[64]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms A and C who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for pola and rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Arms A and C, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL
Number of subjects analysed	31	30
Units: h*ug/mL
geometric mean (geometric coefficient of variation)
acMMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Total Ab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=31,30)	3.29 ( 73.3 )	3.62 ( 78.5 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D

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End point title

Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D ^[65]

End point description

Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arms B and D, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm B (Phase II Randomisation): BR in FL	Arm D (Phase II Randomisation): BR in DLBCL
Number of subjects analysed	33	29
Units: h*ug/mL
geometric mean (geometric coefficient of variation)
Bendamustine (n=33,29)	2.86 ( 67.3 )	3.43 ( 97.4 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F

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End point title

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F ^[66]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for pola and obinutuzumab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arms E and F, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	15	14
Units: h*ug/mL
geometric mean (geometric coefficient of variation)
acMMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Total Ab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=15,14)	2.88 ( 28.9 )	4.10 ( 67.4 )
Obinutuzumab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)

End point description

PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured. As pre-specified in the protocol the analysis of this endpoint was based on sponsor's discretion however, sponsor opted to not collect data for this endpoint.

End point type

Secondary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks

End point values	Arm H (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	0 ^[67]
Units: ng*day/mL
geometric mean (geometric coefficient of variation)	( )

Notes
[67] - Data was not collected for this endpoint per the sponsor's discretion.

No statistical analyses for this end point

Secondary: Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

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End point title

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a ^[68]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Overall number analysed' is the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for bendamustine and rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ia cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL
Number of subjects analysed	4	6
Units: mL/day/kg
geometric mean (geometric coefficient of variation)
acMMAE (n=4,6)	11.3 ( 12.9 )	15.2 ( 27.9 )
Total Ab (n=4,6)	6.05 ( 4.7 )	8.48 ( 35.2 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase Ib: CL of Polatuzumab vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

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End point title

Phase Ib: CL of Polatuzumab vedotin, Bendamustine, and Obinutuzumab in Cohort 1b ^[69]

End point description

PK of three polatuzumab vedotin-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for bendamustine and obinutuzumab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ia cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL
Number of subjects analysed	6	6
Units: mL/day/kg
geometric mean (geometric coefficient of variation)
acMMAE (n=5,6)	12.3 ( 34.9 )	12.1 ( 17.0 )
Total Ab (n=6,6)	6.76 ( 30.6 )	7.17 ( 22.2 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Obinutuzumab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

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End point title

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C ^[70]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms A and B who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for pola and rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL
Number of subjects analysed	30	29
Units: Liters per hour (L/h)
geometric mean (geometric coefficient of variation)
acMMAE(n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Total Ab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=30,29)	47.9 ( 60.8 )	42.6 ( 66.4 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: CL of Bendamustine and Rituximab in Arms B and D

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End point title

Phase II: CL of Bendamustine and Rituximab in Arms B and D ^[71]

End point description

PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. Overall Number Analysed are the number of participants with data available for analysis. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arms B and D hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm B (Phase II Randomisation): BR in FL	Arm D (Phase II Randomisation): BR in DLBCL
Number of subjects analysed	32	29
Units: L/h
geometric mean (geometric coefficient of variation)
Bendamustine (n=32,29)	54.4 ( 60.9 )	46.4 ( 93.9 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

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End point title

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F ^[72]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for polatuzumab and obinutuzumab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	15	14
Units: L/h
geometric mean (geometric coefficient of variation)
acMMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Total Ab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Uncojugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=15,14)	61.3 ( 33.4 )	39.9 ( 76.1 )
Obinutuzumab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)

End point description

End point type

Secondary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	0 ^[73]
Units: mL/day/kg
geometric mean (geometric coefficient of variation)	( )

Notes
[73] - Data was not collected for this endpoint per the sponsor's discretion.

No statistical analyses for this end point

Secondary: Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a

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End point title

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a ^[74]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Overall number analysed' is the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for bendamustine and rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL
Number of subjects analysed	4	6
Units: mL/kg
geometric mean (geometric coefficient of variation)
acMMAE (n=4,6)	73.0 ( 22.3 )	82.7 ( 33.2 )
Total Ab (n=4,6)	82.3 ( 9.1 )	76.6 ( 25.7 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

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End point title

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b ^[75]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for bendamustine and obinutuzumab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase Ib cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL
Number of subjects analysed	6	6
Units: mL/kg
arithmetic mean (standard deviation)
acMMAE (n=5,6)	77.2 ( 38.8 )	64.7 ( 23.0 )
Total Ab (n=6,6)	87.5 ( 38.5 )	87.9 ( 24.7 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Obinutuzumab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

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End point title

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C ^[76]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms A and C who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analysed' are the number of participants with data available for analysis. 'Number Analysed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for polatuzumab and rituximab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL
Number of subjects analysed	29	29
Units: Litres
geometric mean (geometric coefficient of variation)
acMMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Total Ab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=29,29)	36.5 ( 86.4 )	34.3 ( 57.7 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: Vss of Bendamustine and Rituximab in Arms B and D

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End point title

Phase II: Vss of Bendamustine and Rituximab in Arms B and D ^[77]

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm B (Phase II Randomisation): BR in FL	Arm D (Phase II Randomisation): BR in DLBCL
Number of subjects analysed	31	24
Units: Litres
geometric mean (geometric coefficient of variation)
Bendamustine (n=31,24)	44.9 ( 69.6 )	33.2 ( 62.9 )
Rituximab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

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End point title

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F ^[78]

End point description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Here, 999999: participants were not analysed for this PK endpoint at the given timepoint. PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. Overall number analyzed are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for pola and obinutuzumab.

End point type

Secondary

End point timeframe

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Notes
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for Phase II cohorts, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	14	12
Units: Litres
geometric mean (geometric coefficient of variation)
acMMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Total Ab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Unconjugated MMAE (n=0,0)	999999 ( 999999 )	999999 ( 999999 )
Bendamustine (n=14,12)	51.2 ( 33.6 )	31.5 ( 68.1 )
Obinutuzumab (n=0,0)	999999 ( 999999 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)

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End point title

Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)

End point description

End point type

Secondary

End point timeframe

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

End point values	Arm G (Phase II NF Cohort): Pola+BR in DLBCL
Number of subjects analysed	0 ^[79]
Units: milliliters per kilogram (mL/kg)
geometric mean (geometric coefficient of variation)	( )

Notes
[79] - Data was not collected for this endpoint per the sponsor's discretion.

No statistical analyses for this end point

Secondary: Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F

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End point title

Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F ^[80]

End point description

The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. Each item is scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. ITT population included all randomized participants in Arms A-F (Phase II) irrespective of whether or not they received the study treatment. Here, 'Overall Number Analysed' =number of participants with data available for analysis. 'Number Analysed'=number of participants evaluable for this outcome measure. Here, 99999= SD is not evaluable when only one participant is analysed. 999999= participants were not analysed for this PK endpoint at the given timepoint. Participants from Arm F did not answer a sufficient number of questions at both baseline and end of treatment visit therefore the average score could not be calculated. Scores were averaged at each week.

End point type

Secondary

End point timeframe

Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only for arms A-F, hence no descriptive statistics were planned for other cohorts for this endpoint.

End point values	Arm A (Phase II Randomisation): Pola+BR in FL	Arm B (Phase II Randomisation): BR in FL	Arm C (Phase II Randomisation): Pola+BR in DLBCL	Arm D (Phase II Randomisation): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL
Number of subjects analysed	15	14	11	12	5	0 ^[81]
Units: Points on scale
arithmetic mean (standard deviation)
Baseline (n=15,14,11,12,5,0)	0.2 ( 0.3 )	0.5 ( 1.1 )	0.4 ( 0.6 )	0.6 ( 0.7 )	0.8 ( 1.6 )	( )
Week 1 (n=2,0,0,01,0)	0.3 ( 0.4 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 99999 )	( )
Week 2 (n=13,13,10,11,3,0)	0.3 ( 0.4 )	0.5 ( 1.3 )	0.3 ( 0.4 )	1.0 ( 1.1 )	0.2 ( 0.2 )	( )
Week 3 (n=15,13,7,10,4,0)	0.2 ( 0.5 )	0.7 ( 1.5 )	0.1 ( 0.1 )	0.9 ( 0.1 )	0.0 ( 0.1 )	( )
Week 4 (n=12,13,8,9,5,0)	0.1 ( 0.2 )	0.8 ( 1.8 )	0.3 ( 0.3 )	0.7 ( 0.8 )	0.2 ( 0.4 )	( )
Week 5 (n=14,13,8,8,4,0)	0.2 ( 0.3 )	0.6 ( 1.4 )	0.3 ( 0.5 )	0.6 ( 0.6 )	0.1 ( 0.2 )	( )
Week 6 (n=12,13,8,8,4,0)	0.2 ( 0.4 )	0.8 ( 1.8 )	0.3 ( 0.5 )	0.7 ( 1.0 )	0.1 ( 0.3 )	( )
Week 7 (n=11,11,8,8,4,0)	0.3 ( 0.4 )	0.9 ( 1.9 )	0.2 ( 0.3 )	0.4 ( 0.6 )	0.0 ( 0.1 )	( )
Week 8 (n=13,12,7,7,4,0)	0.3 ( 0.4 )	0.8 ( 1.8 )	0.2 ( 0.5 )	0.6 ( 0.9 )	0.2 ( 0.4 )	( )
Week 9 (n=14,14,7,6,5,0)	0.4 ( 0.9 )	0.5 ( 0.9 )	0.2 ( 0.3 )	0.5 ( 0.7 )	0.1 ( 0.3 )	( )
Week 10 (n=12,13,7,6,3,0)	0.5 ( 0.9 )	0.4 ( 0.8 )	0.1 ( 0.1 )	0.2 ( 0.4 )	0.1 ( 0.2 )	( )
Week 11 (n=14,13,8,6,5,0)	0.5 ( 1.0 )	0.5 ( 0.9 )	0.2 ( 0.2 )	0.4 ( 0.6 )	0.1 ( 0.1 )	( )
Week 12 (n=13,12,6,5,3,0)	0.5 ( 1.4 )	0.9 ( 2.0 )	0.3 ( 0.4 )	0.3 ( 0.6 )	0.2 ( 0.2 )	( )
Week 13 (n=12,14,7,5,4,0)	0.7 ( 1.2 )	0.6 ( 1.6 )	0.3 ( 0.4 )	0.2 ( 0.4 )	0.3 ( 0.4 )	( )
Week 14 (n=12,11,7,5,5,0)	0.6 ( 1.2 )	0.7 ( 1.8 )	0.3 ( 0.3 )	0.4 ( 0.6 )	0.2 ( 0.4 )	( )
Week 15 (n=11,12,7,5,3,0)	0.2 ( 0.3 )	0.7 ( 1.7 )	0.4 ( 0.5 )	0.4 ( 0.4 )	0.9 ( 1.6 )	( )
Week 16 (n=11,11,5,5,5,0)	0.4 ( 0.5 )	0.8 ( 1.8 )	0.4 ( 0.4 )	0.4 ( 0.5 )	0.3 ( 0.7 )	( )
Week 17 (n=11,11,6,5,4,0)	0.2 ( 0.3 )	0.8 ( 1.8 )	0.5 ( 0.7 )	0.4 ( 0.6 )	0.3 ( 0.5 )	( )
Week 18 (n=10,11,6,2,4,0)	0.2 ( 0.3 )	0.7 ( 1.8 )	0.3 ( 0.4 )	0.1 ( 0.1 )	0.3 ( 0.5 )	( )
Week 19 (n=12,9,6,4,4,0)	0.2 ( 0.3 )	0.8 ( 2.0 )	0.4 ( 0.7 )	0.5 ( 0.8 )	0.3 ( 0.5 )	( )
Week 20 (n=11,9,5,3,4,0)	0.0 ( 0.2 )	0.8 ( 1.9 )	0.6 ( 0.8 )	0.1 ( 0.1 )	0.3 ( 0.4 )	( )
Week 21 (n=7,10,5,3,4,0)	0.3 ( 0.3 )	0.9 ( 1.9 )	0.5 ( 0.5 )	0.1 ( 0.1 )	0.3 ( 0.3 )	( )
Week 22 (n=9,9,3,1,3,0)	0.2 ( 0.2 )	0.8 ( 2.0 )	0.9 ( 1.5 )	0.0 ( 99999 )	0.5 ( 0.6 )	( )
Week 23 (n=7,9,7,1,3,0)	0.2 ( 0.3 )	0.8 ( 2.2 )	0.6 ( 0.7 )	0.0 ( 99999 )	0.5 ( 0.6 )	( )
Week 24 (n=7,8,7,2,4,0)	0.4 ( 0.6 )	1.0 ( 2.3 )	0.5 ( 0.7 )	0.0 ( 0.1 )	0.3 ( 0.3 )	( )
Week 25 (n=8,7,6,1,2,0)	0.2 ( 0.2 )	0.2 ( 0.2 )	0.3 ( 0.4 )	0.0 ( 99999 )	0.1 ( 0.1 )	( )
Week 26 (n=7,7,6,2,3,0)	0.6 ( 0.8 )	3.3 ( 4.4 )	0.4 ( 0.6 )	0.0 ( 99999 )	999999 ( 999999 )	( )
Week 27 (n=5,2,7,1,0,0)	0.3 ( 0.3 )	1.1 ( 2.5 )	0.5 ( 0.6 )	0.1 ( 0.1 )	0.4 ( 0.4 )	( )
Week 28 (n=8,6,7,1,2,0)	0.5 ( 0.6 )	1.2 ( 2.6 )	0.5 ( 0.7 )	0.0 ( 99999 )	0.1 ( 0.2 )	( )
Week 29 (n=8,7,7,1,3,0)	0.2 ( 0.2 )	0.8 ( 2.1 )	0.7 ( 0.7 )	0.0 ( 99999 )	0.1 ( 0.2 )	( )
Week 30 (n=6,8,4,1,2,0)	0.7 ( 1.1 )	0.7 ( 1.9 )	0.8 ( 0.8 )	0.0 ( 99999 )	0.1 ( 0.1 )	( )
Week 31 (n=7,4,3,1,3,0)	0.3 ( 0.3 )	0.0 ( 0.1 )	1.3 ( 0.9 )	0.0 ( 99999 )	0.1 ( 0.1 )	( )
Week 32 (n=5,6,4,0,2,0)	0.4 ( 0.4 )	0.1 ( 0.1 )	1.0 ( 0.9 )	999999 ( 999999 )	0.2 ( 0.3 )	( )
Week 33 (n=4,6,4,0,3,0)	0.3 ( 0.3 )	0.1 ( 0.2 )	1.0 ( 1.0 )	999999 ( 999999 )	0.2 ( 0.2 )	( )
Week 34 (n=6,4,3,0,2,0)	0.2 ( 0.2 )	1.3 ( 2.4 )	0.8 ( 0.5 )	999999 ( 999999 )	0.2 ( 0.3 )	( )
Week 35 (n=4,1,3,2,1,0)	0.3 ( 0.3 )	0.0 ( 99999 )	1.2 ( 0.7 )	0.6 ( 0.9 )	0.4 ( 99999 )	( )
Week 36 (n=3,2,3,0,2,0)	0.5 ( 0.3 )	0.2 ( 0.3 )	1.2 ( 0.6 )	999999 ( 999999 )	0.1 ( 0.2 )	( )
Week 37 (n=3,5,4,0,2,0)	0.4 ( 0.4 )	0.1 ( 0.1 )	1.1 ( 0.8 )	999999 ( 999999 )	0.2 ( 0.3 )	( )
Week 38 (n=3,1,2,0,1,0)	0.4 ( 0.4 )	0.1 ( 99999 )	1.5 ( 0.4 )	999999 ( 999999 )	0.3 ( 99999 )	( )
Week 39 (n=5,1,2,1,1,0)	0.7 ( 0.9 )	0.0 ( 99999 )	1.5 ( 0.5 )	0.0 ( 99999 )	0.3 ( 99999 )	( )
Week 40 (n=3,1,3,0,2,0)	0.5 ( 0.4 )	0.0 ( 99999 )	0.9 ( 0.4 )	999999 ( 999999 )	0.1 ( 0.2 )	( )
Week 41 (n=2,7,4,0,2,0)	0.6 ( 0.6 )	0.7 ( 1.6 )	1.4 ( 1.2 )	999999 ( 999999 )	0.3 ( 0.4 )	( )
Week 42 (n=3,1,1,0,1,0)	0.5 ( 0.5 )	0.0 ( 99999 )	0.3 ( 99999 )	9999 ( 9999 )	0.5 ( 99999 )	( )
Week 43 (n=4,1,1,1,0)	0.3 ( 0.4 )	0.0 ( 99999 )	0.6 ( 99999 )	0.0 ( 99999 )	0.4 ( 99999 )	( )
Week 44 (n=1,1,2,0,1,0)	1.6 ( 99999 )	0.0 ( 99999 )	0.2 ( 0.3 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 45 (n=3,7,2,0,2,0)	0.8 ( 0.7 )	0.1 ( 0.2 )	1.0 ( 1.2 )	999999 ( 999999 )	0.3 ( 0.4 )	( )
Week 46 (n=2,1,1,0,1,0)	1.1 ( 0.7 )	0.1 ( 99999 )	0.2 ( 99999 )	999999 ( 999999 )	0.5 ( 99999 )	( )
Week 47 (n=4,1,1,0,1,0)	0.4 ( 0.6 )	0.0 ( 99999 )	0.1 ( 99999 )	999999 ( 999999 )	0.8 ( 999999 )	( )
Week 48 (n=0,2,3,0,1,0)	999999 ( 9999999999 )	0.8 ( 0.9 )	0.2 ( 0.2 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 49 (n=2,7,2,0,2,0)	0.6 ( 0.6 )	0.0 ( 0.0 )	1.1 ( 1.4 )	999999 ( 999999999 )	0.3 ( 0.4 )	( )
Week 50 (n=2,1,1,0,1,0)	1.0 ( 0.2 )	0.1 ( 99999 )	0.2 ( 99999 )	999999 ( 999999 )	0.5 ( 99999 )	( )
Week 51 (n=2,1,1,0,1,0)	0.1 ( 0.2 )	0.0 ( 99999 )	0.2 ( 99999 )	999999 ( 999999 )	0.5 ( 99999 )	( )
Week 52 (n=1,2,1,0,1,0)	0.4 ( 99999 )	0.4 ( 0.5 )	0.2 ( 99999 )	999999 ( 999999 )	0.5 ( 99999 )	( )
Week 53 (n=1,5,1,0,2,0)	0.2 ( 99999 )	0.7 ( 1.5 )	0.2 ( 99999 )	999999 ( 999999 )	0.2 ( 0.3 )	( )
Week 54 (n=2,1,1,0,1,0)	0.8 ( 0.6 )	0.0 ( 99999 )	0.2 ( 99999 )	999999 ( 999999 )	0.5 ( 99999 )	( )
Week 55 (n=2,1,1,0,1,0)	0.3 ( 0.5 )	0.2 ( 99999 )	0.2 ( 99999 )	999999 ( 999999 )	0.5 ( 99999 )	( )
Week 56 (n=2,1,2,0,0,0)	0.6 ( 0.3 )	0.2 ( 99999 )	0.0 ( 0.1 )	999999 ( 999999 )	999999 ( 999999 )	( )
Week 57 (n=1,6,2,0,2,0)	0.3 ( 99999 )	0.0 ( 0.0 )	1.5 ( 2.1 )	999999 ( 999999 )	0.2 ( 0.3 )	( )
Week 58 (n=4,0,1,0,1,0)	0.7 ( 0.6 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 59 (n=2,1,1,0,1,0)	0.0 ( 0.1 )	0.0 ( 99999 )	0.0 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 60 (n=1,0,1,0,0,0)	0.4 ( 99999 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	( )
Week 61 (n=3,6,2,0,2,0)	0.4 ( 0.3 )	0.3 ( 0.5 )	1.5 ( 2.1 )	999999 ( 999999 )	0.3 ( 0.5 )	( )
Week 62 (n=2,0,1,0,1,0)	0.7 ( 1.0 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 63 (n=3,1,1,0,1,0)	0.4 ( 0.7 )	0.0 ( 99999 )	0.0 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 64 (n=1,1,2,0,1,0)	0.4 ( 99999 )	1.1 ( 99999 )	0.1 ( 0.2 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 65 (n=2,4,3,0,1,0)	0.2 ( 0.0 )	0.0 ( 0.0 )	0.8 ( 1.3 )	999999 ( 999999 )	0.0 ( 99999 )	( )
Week 66 (n=3,0,1,0,1,0)	0.6 ( 0.7 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 67 (n=2,0,1,0,1,0)	0.2 ( 0.3 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.9 ( 99999 )	( )
Week 68 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	1.2 ( 99999 )	( )
Week 69 (n=1,5,2,0,1,0)	0.2 ( 99999 )	0.3 ( 0.5 )	1.5 ( 2.1 )	999999 ( 999999 )	0.0 ( 99999 )	( )
Week 70 (n=2,0,1,0,1,0)	0.7 ( 1.0 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	1.0 ( 99999 )	( )
Week 71 (n=2,0,1,0,1,0)	0.1 ( 0.1 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 72 (n=0,1,1,01,0)	999999 ( 999999 )	1.2 ( 99999 )	0.0 ( 99999 )	999999 ( 999999 )	0.9 ( 99999 )	( )
Week 73 (n=2,3,2,0,1,0)	0.4 ( 0.3 )	0.0 ( 0.0 )	1.3 ( 1.8 )	999999 ( 999999 )	0.0 ( 99999 )	( )
Week 74 (n=3,0,1,0,1,0)	1.3 ( 0.7 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 9999999999 )	0.8 ( 99999 )	( )
Week 75 (n=2,0,1,0,1,0)	0.2 ( 0.0 )	999999 ( 999999 )	0.0 ( 99999 )	9999 ( 9999 )	1.1 ( 99999 )	( )
Week 76 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 77 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	1.5 ( 99999 )	9999 ( 9999 )	0.9 ( 99999 )	( )
Week 78 (n=1,0,1,0,0,0)	0.7 ( 99999 )	999999 ( 999999 )	1.4 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	( )
Week 79 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	1.4 ( 99999 )	9999 ( 9999 )	0.8 ( 99999 )	( )
Week 80 (n=1,0,1,01,0)	0.0 ( 99999 )	999999 ( 999999 )	1.1 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 81 (n=0,0,1,0,0,0)	999999 ( 999999 )	999999 ( 999999 )	0.6 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	( )
Week 82 (n=0,0,1,0,0,0)	9999999999 ( 999999 )	999999 ( 999999 )	0.6 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	( )
Week 83 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.6 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 84 (n=1,0,1,0,0,0)	0.0 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	( )
Week 85 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.6 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 86 (n=1,0,1,0,1,0)	0.6 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	999999 ( 999999 )	0.6 ( 99999 )	( )
Week 89 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 90 (n=0,0,0,0,1,0)	0.7 ( 99999 )	999999 ( 999999 )	0.5 ( 999999 )	999999 ( 9999 )	0.7 ( 99999 )	( )
Week 91 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 9999 )	0.0 ( 999999 )	999999 ( 9999 )	0.7 ( 99999 )	( )
Week 92 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 93 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.1 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 94 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 95 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.5 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 96 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 97 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.2 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 98 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.0 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 99 (n=0,0,1,0,1,0)	0.6 ( 1.8 )	0.6 ( 1.8 )	0.1 ( 99999 )	0.8 ( 1.0 )	0.7 ( 99999 )	( )
Week 100 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.3 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 101 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 102 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.2 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 103 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.3 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 104 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.2 ( 99999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 105 (n=0,0,1,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	0.1 ( 99999 )	999999 ( 999999 )	0.8 ( 99999 )	( )
Week 107 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
Week 108 (n=0,0,0,0,1,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.7 ( 99999 )	( )
End of Treatment (n=15,14,11,12,5,0)	0.4 ( 0.6 )	0.6 ( 1.8 )	0.5 ( 0.8 )	0.8 ( 1.0 )	0.1 ( 0.2 )	( )

Notes
[81] - No participants were analysed from this Arm.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the study start up to the end of the study (up to approximately 84 months)

Adverse event reporting additional description

Serious and non-serious adverse events were reported for safety population. Safety population=participants who received at least one dose of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL

Reporting group description

Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine, 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL

Reporting group description

Reporting group title

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL

Reporting group description

Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL

Reporting group description

Reporting group title

Arm A (Phase II Randomization): Pola+BR in FL

Reporting group description

Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Arm B (Phase II Randomization): BR in FL

Reporting group description

Reporting group title

Arm C (Phase II Randomization): Pola+BR in DLBCL

Reporting group description

Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola.

Reporting group title

Arm D (Phase II Randomization): BR in DLBCL

Reporting group description

Reporting group title

Arm E (Phase II Expansion): Pola+BG in FL

Reporting group description

Reporting group title

Arm F (Phase II Expansion): Pola+BG in DLBCL

Reporting group description

Reporting group title

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Reporting group description

Serious adverse events	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomization): Pola+BR in FL	Arm B (Phase II Randomization): BR in FL	Arm C (Phase II Randomization): Pola+BR in DLBCL	Arm D (Phase II Randomization): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 6 (66.67%)	4 / 6 (66.67%)	2 / 6 (33.33%)	5 / 6 (83.33%)	25 / 38 (65.79%)	12 / 41 (29.27%)	27 / 39 (69.23%)	24 / 39 (61.54%)	8 / 20 (40.00%)	13 / 20 (65.00%)	57 / 106 (53.77%)
number of deaths (all causes)	2	2	2	4	16	11	26	30	3	18	65
number of deaths resulting from adverse events	0	0	0	1	1	1	3	2	1	0	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ADENOCARCINOMA GASTRIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ADENOCARCINOMA OF COLON
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENDOMETRIAL ADENOCARCINOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENDOMETRIAL CANCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INTESTINAL ADENOCARCINOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LYMPHOCYTIC LEUKAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MALIGNANT MELANOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
MYELODYSPLASTIC SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PROSTATE CANCER
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SQUAMOUS CELL CARCINOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
EPIGLOTTIC CANCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PANCREATIC CARCINOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RENAL CANCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
DEEP VEIN THROMBOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DISTRIBUTIVE SHOCK
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
HYPOTENSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THROMBOPHLEBITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEATH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
GENERAL PHYSICAL HEALTH DETERIORATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
MULTIPLE ORGAN DYSFUNCTION SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
OEDEMA PERIPHERAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 38 (5.26%)	1 / 41 (2.44%)	5 / 39 (12.82%)	0 / 39 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	7 / 106 (6.60%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	1 / 2	1 / 1	2 / 5	0 / 0	0 / 0	0 / 3	3 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SUDDEN DEATH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
BRONCHOPNEUMOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DYSPNOEA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HAEMOPTYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
HYPERVENTILATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LUNG DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PLEURAL EFFUSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMOTHORAX
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PULMONARY OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY FAILURE
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
BLOOD CREATININE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS WORSENED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MORAXELLA TEST POSITIVE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TRANSAMINASES INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
WEIGHT DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
FALL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HEAD INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
POST PROCEDURAL FEVER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL FLUTTER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC ARREST
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
CARDIOMYOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MYOCARDIAL ISCHAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SUPRAVENTRICULAR TACHYCARDIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TACHYCARDIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL THROMBOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
CAROTID ARTERY OCCLUSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CEREBRAL HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
CEREBRAL INFARCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CEREBRAL ISCHAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CEREBROVASCULAR ACCIDENT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
HAEMORRHAGE INTRACRANIAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
HYDROCEPHALUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
LEUKOENCEPHALOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
SEIZURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VOCAL CORD PARALYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BRAIN OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	6 / 38 (15.79%)	1 / 41 (2.44%)	4 / 39 (10.26%)	4 / 39 (10.26%)	2 / 20 (10.00%)	2 / 20 (10.00%)	9 / 106 (8.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	7 / 9	0 / 1	3 / 4	2 / 4	3 / 3	2 / 2	3 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LEUKOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LYMPHOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	1 / 39 (2.56%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 1	1 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PANCYTOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THROMBOCYTOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ASCITES
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COLITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CONSTIPATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	4 / 4	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DUODENAL ULCER HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTERITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
GASTRITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MOUTH ULCERATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
OBSTRUCTION GASTRIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PANCREATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SMALL INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS HAEMORRHAGIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
HEPATIC CIRRHOSIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPERTRANSAMINASAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ISCHAEMIC HEPATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
DRUG ERUPTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RASH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RASH ERYTHEMATOUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	2 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HAEMATURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYDRONEPHROSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RENAL FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
BACK PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FLANK PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MUSCULAR WEAKNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
ABDOMINAL ABSCESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ABDOMINAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ARTHRITIS BACTERIAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BACTERAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BACTERIAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BRONCHITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CEREBRAL TOXOPLASMOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIAL SEPSIS
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE COLITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS CHORIORETINITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS COLITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS ENTERITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEVICE RELATED INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIVERTICULITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS VIRAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ESCHERICHIA BACTERAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
GASTROENTERITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL BACTERIAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
GIARDIASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HEPATITIS E
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HERPES VIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HERPES ZOSTER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HUMAN ANAPLASMOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFECTED LYMPHOCELE
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
LARGE INTESTINE INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MENINGOENCEPHALITIS HERPETIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIC SEPSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
OESOPHAGEAL CANDIDIASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ORAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PARONYCHIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PLEURAL INFECTION BACTERIAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMOCYSTIS JIROVECII PNEUMONIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	7 / 38 (18.42%)	1 / 41 (2.44%)	4 / 39 (10.26%)	4 / 39 (10.26%)	0 / 20 (0.00%)	0 / 20 (0.00%)	6 / 106 (5.66%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2	3 / 8	0 / 1	2 / 5	0 / 4	0 / 0	0 / 0	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	1 / 2	0 / 1	0 / 0	0 / 0	1 / 1
PNEUMONIA BACTERIAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA CYTOMEGALOVIRAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA FUNGAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
PNEUMONIA PNEUMOCOCCAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA VIRAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
POST PROCEDURAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
RESPIRATORY SYNCYTIAL VIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION VIRAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RHINOVIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	2 / 39 (5.13%)	2 / 39 (5.13%)	0 / 20 (0.00%)	1 / 20 (5.00%)	7 / 106 (6.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 1	0 / 2	0 / 2	0 / 0	0 / 1	7 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 2	0 / 0	0 / 1	2 / 2
SEPTIC SHOCK
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	2 / 41 (4.88%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
UROSEPSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 PNEUMONIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DISSEMINATED VARICELLA ZOSTER VIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VASCULAR ACCESS SITE CELLULITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEHYDRATION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOMAGNESAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TUMOUR LYSIS SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL	Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL	Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL	Arm A (Phase II Randomization): Pola+BR in FL	Arm B (Phase II Randomization): BR in FL	Arm C (Phase II Randomization): Pola+BR in DLBCL	Arm D (Phase II Randomization): BR in DLBCL	Arm E (Phase II Expansion): Pola+BG in FL	Arm F (Phase II Expansion): Pola+BG in DLBCL	Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	38 / 38 (100.00%)	39 / 41 (95.12%)	37 / 39 (94.87%)	36 / 39 (92.31%)	20 / 20 (100.00%)	19 / 20 (95.00%)	103 / 106 (97.17%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HODGKIN'S DISEASE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
MYELODYSPLASTIC SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
TUMOUR PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
ENDOMETRIAL ADENOCARCINOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Vascular disorders
DEEP VEIN THROMBOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0	0	0
FLUSHING
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	3 / 41 (7.32%)	0 / 39 (0.00%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	2	3	0	0	0	3	0	1	2	0	1
HYPOTENSION
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	1 / 41 (2.44%)	2 / 39 (5.13%)	5 / 39 (12.82%)	0 / 20 (0.00%)	3 / 20 (15.00%)	10 / 106 (9.43%)
occurrences all number	1	2	0	0	2	1	2	5	0	4	12
HYPERTENSION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 38 (5.26%)	2 / 41 (4.88%)	2 / 39 (5.13%)	1 / 39 (2.56%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 106 (0.94%)
occurrences all number	0	1	1	0	2	3	2	1	2	2	1
EMBOLISM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	2	0	1	0	1	0
PALLOR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
PHLEBITIS SUPERFICIAL
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	7 / 38 (18.42%)	3 / 41 (7.32%)	4 / 39 (10.26%)	6 / 39 (15.38%)	0 / 20 (0.00%)	3 / 20 (15.00%)	12 / 106 (11.32%)
occurrences all number	1	0	0	1	9	5	4	8	0	3	13
CHILLS
subjects affected / exposed	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 38 (0.00%)	3 / 41 (7.32%)	4 / 39 (10.26%)	3 / 39 (7.69%)	2 / 20 (10.00%)	5 / 20 (25.00%)	2 / 106 (1.89%)
occurrences all number	4	5	2	3	0	3	5	4	2	5	2
DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	1	0
FATIGUE
subjects affected / exposed	4 / 6 (66.67%)	3 / 6 (50.00%)	4 / 6 (66.67%)	2 / 6 (33.33%)	16 / 38 (42.11%)	13 / 41 (31.71%)	14 / 39 (35.90%)	14 / 39 (35.90%)	13 / 20 (65.00%)	12 / 20 (60.00%)	22 / 106 (20.75%)
occurrences all number	5	3	4	2	20	22	20	17	22	15	25
MUCOSAL INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	1	0	0	0	1	2	0	3
OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	3 / 39 (7.69%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	2	3	0	1	0
OEDEMA PERIPHERAL
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	4 / 41 (9.76%)	2 / 39 (5.13%)	2 / 39 (5.13%)	2 / 20 (10.00%)	3 / 20 (15.00%)	6 / 106 (5.66%)
occurrences all number	0	1	0	0	5	4	2	2	2	3	7
PYREXIA
subjects affected / exposed	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	8 / 38 (21.05%)	4 / 41 (9.76%)	10 / 39 (25.64%)	9 / 39 (23.08%)	2 / 20 (10.00%)	8 / 20 (40.00%)	22 / 106 (20.75%)
occurrences all number	4	4	1	2	11	5	14	15	2	9	27
PAIN
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	5 / 106 (4.72%)
occurrences all number	0	2	0	0	0	0	2	1	1	0	5
CATHETER SITE PAIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
CATHETER SITE PRURITUS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
CHEST DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	0	1	1	1	0	1	2
CHEST PAIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	1	0	0	1	0	1	0	0	1	1
EARLY SATIETY
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
GAIT DISTURBANCE
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	1	0	0	0	1	0	1	0	0	1	1
PERIPHERAL SWELLING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	0	2	0	1	0	0	1	0	0	3
Immune system disorders
HYPOGAMMAGLOBULINAEMIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	1	0	0	0	0	1	0	1	0	1
HYPERSENSITIVITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	1	1	0	0	1	0	2
Reproductive system and breast disorders
ERECTILE DYSFUNCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0	0	0	0
TESTICULAR PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0
TESTICULAR SWELLING
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
VAGINAL DISCHARGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
VAGINAL HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	6 / 38 (15.79%)	3 / 41 (7.32%)	6 / 39 (15.38%)	8 / 39 (20.51%)	2 / 20 (10.00%)	3 / 20 (15.00%)	13 / 106 (12.26%)
occurrences all number	1	6	1	0	7	3	6	10	2	3	16
DYSPHONIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	1	0	0	1	0	0	1	2	0	1
DYSPNOEA
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 6 (33.33%)	4 / 38 (10.53%)	4 / 41 (9.76%)	3 / 39 (7.69%)	2 / 39 (5.13%)	7 / 20 (35.00%)	6 / 20 (30.00%)	3 / 106 (2.83%)
occurrences all number	0	2	3	3	4	4	3	2	7	7	4
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	1 / 39 (2.56%)	2 / 39 (5.13%)	1 / 20 (5.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	0	0	1	0	1	1	1	2	1	1	2
HYPOXIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	1	0	0	1	0	0	1	0
NASAL CONGESTION
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	2 / 41 (4.88%)	0 / 39 (0.00%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	1	1	0	0	2	2	0	0	2	0	1
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	4 / 38 (10.53%)	2 / 41 (4.88%)	2 / 39 (5.13%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	5 / 106 (4.72%)
occurrences all number	0	1	0	0	5	3	2	1	2	0	6
PLEURAL EFFUSION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	3 / 39 (7.69%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	2	0	0	1	0	1	1	3	0	1	1
PRODUCTIVE COUGH
subjects affected / exposed	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	2 / 39 (5.13%)	2 / 39 (5.13%)	3 / 20 (15.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	2	3	0	0	0	1	2	2	4	0	3
RHINORRHOEA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	2 / 39 (5.13%)	1 / 20 (5.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	1	0	0	1	0	1	2	1	0	3
THROAT IRRITATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	3 / 41 (7.32%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	3
UPPER-AIRWAY COUGH SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	2	0	0
BRONCHOSPASM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
HAEMOPTYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
HICCUPS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	1	1	0	1	0	0	0	1
NASAL DISCHARGE DISCOLOURATION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
ORGANISING PNEUMONIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
PNEUMONITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0	0	0	0
PULMONARY EMBOLISM
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	2
PULMONARY OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
RHINITIS ALLERGIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0
SINUS CONGESTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0
SINUS PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
TACHYPNOEA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	1	0	1	0	1	0	0	0
Psychiatric disorders
ANXIETY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 38 (5.26%)	2 / 41 (4.88%)	3 / 39 (7.69%)	2 / 39 (5.13%)	1 / 20 (5.00%)	2 / 20 (10.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	1	3	2	3	2	1	2	4
DEPRESSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	2 / 41 (4.88%)	1 / 39 (2.56%)	3 / 39 (7.69%)	2 / 20 (10.00%)	2 / 20 (10.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	3	2	1	3	2	2	1
INSOMNIA
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 6 (16.67%)	3 / 38 (7.89%)	3 / 41 (7.32%)	3 / 39 (7.69%)	0 / 39 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	8 / 106 (7.55%)
occurrences all number	1	1	3	1	3	3	3	0	2	1	10
CONFUSIONAL STATE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	1
DELIRIUM
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
IRRITABILITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
MENTAL STATUS CHANGES
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
SUICIDAL IDEATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	0	1	0	1	0	6	0	4
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	5 / 106 (4.72%)
occurrences all number	0	1	0	0	1	0	2	0	3	0	6
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	7 / 106 (6.60%)
occurrences all number	0	0	0	0	2	0	1	1	6	0	11
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	5	0	0
BLOOD CREATININE INCREASED
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 38 (7.89%)	2 / 41 (4.88%)	2 / 39 (5.13%)	4 / 39 (10.26%)	3 / 20 (15.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	1	1	0	1	6	2	2	6	3	0	9
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	6 / 106 (5.66%)
occurrences all number	0	0	0	0	2	2	0	0	0	0	8
C-REACTIVE PROTEIN INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	2
LIPASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	3 / 39 (7.69%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	0	2	1	5	0	1	0	7
HAEMOGLOBIN DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	4	0	0	0
LYMPHOCYTE COUNT DECREASED
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	1 / 39 (2.56%)	3 / 39 (7.69%)	2 / 20 (10.00%)	0 / 20 (0.00%)	8 / 106 (7.55%)
occurrences all number	1	0	2	0	10	0	1	5	6	0	16
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	2 / 41 (4.88%)	1 / 39 (2.56%)	2 / 39 (5.13%)	0 / 20 (0.00%)	2 / 20 (10.00%)	14 / 106 (13.21%)
occurrences all number	0	0	0	0	15	2	1	2	0	2	37
PLATELET COUNT DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	3 / 38 (7.89%)	0 / 41 (0.00%)	4 / 39 (10.26%)	2 / 39 (5.13%)	1 / 20 (5.00%)	0 / 20 (0.00%)	8 / 106 (7.55%)
occurrences all number	0	0	1	0	18	0	5	5	1	0	11
WEIGHT DECREASED
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	3 / 38 (7.89%)	0 / 41 (0.00%)	5 / 39 (12.82%)	2 / 39 (5.13%)	2 / 20 (10.00%)	1 / 20 (5.00%)	14 / 106 (13.21%)
occurrences all number	2	0	2	0	3	0	5	2	3	1	14
WEIGHT INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	2
WHITE BLOOD CELL COUNT DECREASED
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	0 / 41 (0.00%)	1 / 39 (2.56%)	4 / 39 (10.26%)	3 / 20 (15.00%)	1 / 20 (5.00%)	9 / 106 (8.49%)
occurrences all number	1	0	0	0	16	0	1	6	7	1	29
AMYLASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	0	2	0	2	0	0	0	4
BLOOD CALCIUM DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0
BLOOD MAGNESIUM DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0
BLOOD PHOSPHORUS DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	0
EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS WORSENED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
HEPATIC ENZYME INCREASED
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
LIVER FUNCTION TEST ABNORMAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	2
NEUTROPHIL COUNT INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
TRANSAMINASES INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0
TROPONIN I INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
TROPONIN INCREASED
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
FALL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	3	0	1	0	0	2	4
INFUSION RELATED REACTION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	5 / 38 (13.16%)	5 / 41 (12.20%)	1 / 39 (2.56%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	1	0	6	6	3	1	1	0	0
LIMB INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0
ARTHROPOD BITE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
COMMINUTED FRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
WOUND
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 38 (2.63%)	2 / 41 (4.88%)	0 / 39 (0.00%)	3 / 39 (7.69%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	1	0	0	1	1	2	0	3	0	0	2
TACHYCARDIA
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	1 / 41 (2.44%)	2 / 39 (5.13%)	2 / 39 (5.13%)	0 / 20 (0.00%)	1 / 20 (5.00%)	6 / 106 (5.66%)
occurrences all number	1	1	0	1	0	1	3	2	0	1	6
BUNDLE BRANCH BLOCK RIGHT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
SINUS TACHYCARDIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	1	0	1	1	1	0
VENTRICULAR TACHYCARDIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
ATRIOVENTRICULAR BLOCK FIRST DEGREE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0
Nervous system disorders
DIZZINESS
subjects affected / exposed	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	4 / 38 (10.53%)	5 / 41 (12.20%)	5 / 39 (12.82%)	3 / 39 (7.69%)	3 / 20 (15.00%)	1 / 20 (5.00%)	10 / 106 (9.43%)
occurrences all number	1	2	1	1	4	5	5	3	3	1	11
DYSGEUSIA
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	2 / 41 (4.88%)	1 / 39 (2.56%)	0 / 39 (0.00%)	3 / 20 (15.00%)	1 / 20 (5.00%)	5 / 106 (4.72%)
occurrences all number	2	0	0	0	3	2	1	0	3	1	5
HEADACHE
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	8 / 38 (21.05%)	5 / 41 (12.20%)	3 / 39 (7.69%)	2 / 39 (5.13%)	6 / 20 (30.00%)	3 / 20 (15.00%)	12 / 106 (11.32%)
occurrences all number	3	2	0	0	8	6	3	3	6	4	14
HYPOAESTHESIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	1 / 41 (2.44%)	2 / 39 (5.13%)	0 / 39 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	2	0	0	0	2	1	2	0	5	1	0
NEUROPATHY PERIPHERAL
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	6 / 38 (15.79%)	5 / 41 (12.20%)	9 / 39 (23.08%)	1 / 39 (2.56%)	5 / 20 (25.00%)	1 / 20 (5.00%)	15 / 106 (14.15%)
occurrences all number	0	1	1	0	9	5	10	1	5	1	16
PARAESTHESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 6 (50.00%)	5 / 38 (13.16%)	2 / 41 (4.88%)	2 / 39 (5.13%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	3	8	2	2	0	1	0	4
PERIPHERAL MOTOR NEUROPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	1	0
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	5 / 38 (13.16%)	3 / 41 (7.32%)	6 / 39 (15.38%)	0 / 39 (0.00%)	3 / 20 (15.00%)	2 / 20 (10.00%)	5 / 106 (4.72%)
occurrences all number	0	2	1	1	5	3	7	0	3	2	6
POST HERPETIC NEURALGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	2	0
SYNCOPE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	0	0	2	3	0	0	3
AMNESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
DYSKINESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
LETHARGY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	1
NEURALGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	1	0	0
PERONEAL NERVE PALSY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
POLYNEUROPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0
RESTLESS LEGS SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	1	1	0	0	1	0	0	1
SCIATICA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
SINUS HEADACHE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
SOMNOLENCE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1
TASTE DISORDER
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	1
TREMOR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	2 / 41 (4.88%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	0	2	2	1	0	0	0	4
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	6 / 38 (15.79%)	5 / 41 (12.20%)	19 / 39 (48.72%)	10 / 39 (25.64%)	3 / 20 (15.00%)	5 / 20 (25.00%)	27 / 106 (25.47%)
occurrences all number	0	0	2	0	24	5	28	13	7	6	35
LEUKOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	3 / 41 (7.32%)	5 / 39 (12.82%)	4 / 39 (10.26%)	0 / 20 (0.00%)	0 / 20 (0.00%)	7 / 106 (6.60%)
occurrences all number	0	0	0	0	5	4	19	6	0	0	17
LYMPHOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	3 / 41 (7.32%)	5 / 39 (12.82%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	5 / 106 (4.72%)
occurrences all number	0	0	0	0	5	4	6	0	5	0	7
NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 6 (16.67%)	16 / 38 (42.11%)	11 / 41 (26.83%)	21 / 39 (53.85%)	14 / 39 (35.90%)	6 / 20 (30.00%)	6 / 20 (30.00%)	35 / 106 (33.02%)
occurrences all number	0	8	4	1	31	18	63	27	10	30	73
PANCYTOPENIA
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	1	1	0	1	0	0	1	0	0	1	2
THROMBOCYTOPENIA
subjects affected / exposed	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 38 (7.89%)	8 / 41 (19.51%)	19 / 39 (48.72%)	11 / 39 (28.21%)	4 / 20 (20.00%)	7 / 20 (35.00%)	19 / 106 (17.92%)
occurrences all number	2	1	2	1	6	13	50	18	4	10	40
COAGULOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	1	0	1	0	1	1
HAEMOLYTIC ANAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
HAEMOLYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
LYMPHADENOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0
IMMUNE THROMBOCYTOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Ear and labyrinth disorders
HYPOACUSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	1
EAR PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	1	0
Eye disorders
EYE DISCHARGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
EYE PRURITUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	1
GLAUCOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
OCULAR HYPERAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
VISION BLURRED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	1	0	0
Gastrointestinal disorders
ABDOMINAL DISTENSION
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 38 (5.26%)	2 / 41 (4.88%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 106 (0.94%)
occurrences all number	1	1	0	1	2	2	1	0	1	2	1
ABDOMINAL PAIN
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	6 / 38 (15.79%)	5 / 41 (12.20%)	3 / 39 (7.69%)	3 / 39 (7.69%)	0 / 20 (0.00%)	2 / 20 (10.00%)	12 / 106 (11.32%)
occurrences all number	1	0	1	1	6	5	3	3	0	2	14
ABDOMINAL PAIN LOWER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0
ABDOMINAL PAIN UPPER
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	1 / 41 (2.44%)	5 / 39 (12.82%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	6 / 106 (5.66%)
occurrences all number	0	1	0	0	4	1	5	2	0	0	7
APHTHOUS ULCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0
CONSTIPATION
subjects affected / exposed	1 / 6 (16.67%)	4 / 6 (66.67%)	3 / 6 (50.00%)	2 / 6 (33.33%)	10 / 38 (26.32%)	8 / 41 (19.51%)	7 / 39 (17.95%)	8 / 39 (20.51%)	7 / 20 (35.00%)	9 / 20 (45.00%)	20 / 106 (18.87%)
occurrences all number	1	7	3	2	10	8	8	9	11	10	27
DIARRHOEA
subjects affected / exposed	2 / 6 (33.33%)	4 / 6 (66.67%)	2 / 6 (33.33%)	4 / 6 (66.67%)	16 / 38 (42.11%)	9 / 41 (21.95%)	16 / 39 (41.03%)	11 / 39 (28.21%)	10 / 20 (50.00%)	11 / 20 (55.00%)	36 / 106 (33.96%)
occurrences all number	5	7	8	4	27	11	28	13	22	18	48
DRY MOUTH
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	3 / 20 (15.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	2	0	0	1	0	1	1	3	0	4
DYSPEPSIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	4 / 38 (10.53%)	6 / 41 (14.63%)	3 / 39 (7.69%)	2 / 39 (5.13%)	3 / 20 (15.00%)	0 / 20 (0.00%)	5 / 106 (4.72%)
occurrences all number	0	0	0	0	6	6	4	2	3	0	6
FLATULENCE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	2 / 20 (10.00%)	2 / 20 (10.00%)	1 / 106 (0.94%)
occurrences all number	0	0	1	0	0	1	1	0	2	2	1
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	2 / 20 (10.00%)	2 / 20 (10.00%)	3 / 106 (2.83%)
occurrences all number	1	0	0	0	1	0	2	0	2	2	3
NAUSEA
subjects affected / exposed	3 / 6 (50.00%)	5 / 6 (83.33%)	3 / 6 (50.00%)	3 / 6 (50.00%)	22 / 38 (57.89%)	13 / 41 (31.71%)	12 / 39 (30.77%)	16 / 39 (41.03%)	11 / 20 (55.00%)	11 / 20 (55.00%)	34 / 106 (32.08%)
occurrences all number	4	7	4	3	35	25	14	19	21	16	38
ODYNOPHAGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	4
STOMATITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	5 / 38 (13.16%)	2 / 41 (4.88%)	3 / 39 (7.69%)	4 / 39 (10.26%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	1	1	1	6	3	4	4	1	1	0
VOMITING
subjects affected / exposed	1 / 6 (16.67%)	5 / 6 (83.33%)	2 / 6 (33.33%)	1 / 6 (16.67%)	7 / 38 (18.42%)	8 / 41 (19.51%)	7 / 39 (17.95%)	5 / 39 (12.82%)	8 / 20 (40.00%)	8 / 20 (40.00%)	17 / 106 (16.04%)
occurrences all number	2	6	3	1	12	11	11	8	10	10	18
ABDOMINAL DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	1
ANAL SPASM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
COLITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	1
DEFAECATION URGENCY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
DIVERTICULUM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
DYSPHAGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	1	0	1	1	0	1	3
GINGIVAL BLEEDING
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
GINGIVAL DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
GINGIVAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	1	1	0	1	0	1
HAEMATEMESIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	1	0
HAEMATOCHEZIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0
HAEMORRHOIDS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	1	0	0	0	1	1	2
LIP DRY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0
MOUTH ULCERATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	2
NONINFECTIVE GINGIVITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
RECTAL DISCHARGE
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
RECTAL HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
ALOPECIA
subjects affected / exposed	0 / 6 (0.00%)	3 / 6 (50.00%)	3 / 6 (50.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	3 / 20 (15.00%)	2 / 20 (10.00%)	1 / 106 (0.94%)
occurrences all number	0	3	3	0	1	0	0	1	3	2	1
DRY SKIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 38 (5.26%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	2	1	1	0	0	0	0
ERYTHEMA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	5 / 106 (4.72%)
occurrences all number	0	1	0	0	1	4	0	0	0	2	10
HYPERHIDROSIS
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	2	0	0	3	1	0	0	0	1	0
NIGHT SWEATS
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	1	1	2	0	1	0	0	1	0	0	3
PRURITUS
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 38 (5.26%)	4 / 41 (9.76%)	5 / 39 (12.82%)	4 / 39 (10.26%)	1 / 20 (5.00%)	0 / 20 (0.00%)	8 / 106 (7.55%)
occurrences all number	1	1	1	1	2	4	6	5	1	0	9
RASH
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	3 / 38 (7.89%)	4 / 41 (9.76%)	2 / 39 (5.13%)	5 / 39 (12.82%)	3 / 20 (15.00%)	3 / 20 (15.00%)	5 / 106 (4.72%)
occurrences all number	2	0	3	2	5	5	2	5	5	3	8
RASH MACULO-PAPULAR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	3 / 41 (7.32%)	1 / 39 (2.56%)	1 / 39 (2.56%)	1 / 20 (5.00%)	2 / 20 (10.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	0	3	1	1	1	2	2
URTICARIA
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	2	0	0	0	0	2	1	0	0	2
DERMATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	1
RASH MACULAR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
SKIN DISCOLOURATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Renal and urinary disorders
DYSURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	0	0	0	0	1	1	0	0	2	1	2
POLLAKIURIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 106 (0.94%)
occurrences all number	1	0	0	0	2	0	1	0	1	2	1
URINARY INCONTINENCE
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	1	0	0	4	0	0	0	0	0	3
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	4
ANURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1
HAEMATURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	0	1	0	1	0	1	4
RENAL FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0
URINARY RETENTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	3 / 41 (7.32%)	5 / 39 (12.82%)	1 / 39 (2.56%)	2 / 20 (10.00%)	1 / 20 (5.00%)	6 / 106 (5.66%)
occurrences all number	0	1	0	0	4	4	5	1	4	1	6
BACK PAIN
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 38 (7.89%)	3 / 41 (7.32%)	1 / 39 (2.56%)	4 / 39 (10.26%)	3 / 20 (15.00%)	2 / 20 (10.00%)	7 / 106 (6.60%)
occurrences all number	0	2	0	1	3	3	1	4	3	2	8
BONE PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	0	0	1	2	1	2	0	0	0	1	2
MUSCULAR WEAKNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	1 / 39 (2.56%)	3 / 20 (15.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences all number	0	0	1	2	1	0	2	1	4	1	3
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	1	0	0	1	0	1	0	0	0	1
MYALGIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	1 / 39 (2.56%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	1	0	0	1	1	1	3	0	0	3
PAIN IN EXTREMITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	2 / 41 (4.88%)	2 / 39 (5.13%)	2 / 39 (5.13%)	1 / 20 (5.00%)	3 / 20 (15.00%)	4 / 106 (3.77%)
occurrences all number	0	0	0	0	3	2	2	2	2	3	4
CERVICAL SPINAL STENOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
GROIN PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1
INTERVERTEBRAL DISC DEGENERATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
MUSCLE SPASMS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	2 / 39 (5.13%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	0	1	2	1	0	1	3
MUSCLE TIGHTNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0
MUSCULOSKELETAL STIFFNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
NECK PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	1	0	2	0	0	2	1
Infections and infestations
BRONCHITIS
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	2 / 41 (4.88%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	2	0	0	3	2	1	0	0	0	2
HERPES VIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	2	0	0
HERPES ZOSTER
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	4 / 38 (10.53%)	2 / 41 (4.88%)	1 / 39 (2.56%)	2 / 39 (5.13%)	1 / 20 (5.00%)	3 / 20 (15.00%)	0 / 106 (0.00%)
occurrences all number	1	1	1	1	4	2	1	3	1	4	0
NASOPHARYNGITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	2 / 41 (4.88%)	1 / 39 (2.56%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	3	3	1	1	0	1	1
ORAL HERPES
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	1 / 41 (2.44%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 106 (1.89%)
occurrences all number	0	1	0	0	3	1	0	2	0	0	2
PNEUMONIA
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 38 (5.26%)	2 / 41 (4.88%)	3 / 39 (7.69%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	6 / 106 (5.66%)
occurrences all number	1	1	0	1	2	2	3	1	1	0	6
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	4 / 38 (10.53%)	2 / 41 (4.88%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	6	2	0	0	0	0	0
SINUSITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	3 / 41 (7.32%)	1 / 39 (2.56%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	2	0	0	3	1	1	2	0	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 38 (7.89%)	7 / 41 (17.07%)	2 / 39 (5.13%)	1 / 39 (2.56%)	5 / 20 (25.00%)	2 / 20 (10.00%)	7 / 106 (6.60%)
occurrences all number	2	1	0	2	3	7	4	1	5	3	10
URINARY TRACT INFECTION
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	0 / 41 (0.00%)	1 / 39 (2.56%)	2 / 39 (5.13%)	2 / 20 (10.00%)	2 / 20 (10.00%)	7 / 106 (6.60%)
occurrences all number	1	2	0	0	3	0	1	2	2	2	8
CANDIDA INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1
CELLULITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	1	1	0	0	0	0
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0
CYSTITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	0
CYTOMEGALOVIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	0
CYTOMEGALOVIRUS VIRAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
EAR INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
ESCHERICHIA URINARY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
FOLLICULITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0	1	0	0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
ORAL CANDIDIASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	2 / 39 (5.13%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 106 (0.94%)
occurrences all number	0	0	0	0	1	1	2	0	3	0	1
RASH PUSTULAR
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
SKIN INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
VASCULAR ACCESS SITE INFECTION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	2 / 6 (33.33%)	2 / 6 (33.33%)	3 / 6 (50.00%)	3 / 6 (50.00%)	10 / 38 (26.32%)	5 / 41 (12.20%)	10 / 39 (25.64%)	8 / 39 (20.51%)	6 / 20 (30.00%)	8 / 20 (40.00%)	27 / 106 (25.47%)
occurrences all number	2	2	3	3	13	5	11	8	7	10	30
DEHYDRATION
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 38 (2.63%)	0 / 41 (0.00%)	2 / 39 (5.13%)	0 / 39 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	2	0	0	1	1	0	2	0	1	1	2
HYPERCALCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	0 / 39 (0.00%)	2 / 39 (5.13%)	0 / 20 (0.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	1	1	0	2	0	0	3
HYPERGLYCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	3 / 38 (7.89%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	0	3	2	9	1	1	0	1	0	3
HYPERURICAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 38 (7.89%)	1 / 41 (2.44%)	1 / 39 (2.56%)	0 / 39 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	0	0	0	0	3	1	1	0	2	0	3
HYPOALBUMINAEMIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 38 (2.63%)	1 / 41 (2.44%)	5 / 39 (12.82%)	2 / 39 (5.13%)	1 / 20 (5.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	1	0	0	0	2	1	7	2	1	0	3
HYPOCALCAEMIA
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 38 (2.63%)	1 / 41 (2.44%)	3 / 39 (7.69%)	1 / 39 (2.56%)	2 / 20 (10.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	2	0	0	1	2	1	5	1	5	0	3
HYPOKALAEMIA
subjects affected / exposed	3 / 6 (50.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	5 / 38 (13.16%)	4 / 41 (9.76%)	4 / 39 (10.26%)	3 / 39 (7.69%)	3 / 20 (15.00%)	5 / 20 (25.00%)	15 / 106 (14.15%)
occurrences all number	3	4	2	2	9	6	7	3	9	5	20
HYPOMAGNESAEMIA
subjects affected / exposed	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 6 (50.00%)	4 / 38 (10.53%)	1 / 41 (2.44%)	1 / 39 (2.56%)	4 / 39 (10.26%)	4 / 20 (20.00%)	1 / 20 (5.00%)	13 / 106 (12.26%)
occurrences all number	2	1	5	3	6	1	1	5	4	1	18
HYPOPHOSPHATAEMIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 38 (5.26%)	1 / 41 (2.44%)	2 / 39 (5.13%)	1 / 39 (2.56%)	2 / 20 (10.00%)	1 / 20 (5.00%)	2 / 106 (1.89%)
occurrences all number	1	0	2	2	6	1	3	1	6	1	5
HYPERPHOSPHATAEMIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
HYPOGLYCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	1 / 39 (2.56%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	1	0	0
HYPONATRAEMIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 38 (5.26%)	1 / 41 (2.44%)	0 / 39 (0.00%)	0 / 39 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	3 / 106 (2.83%)
occurrences all number	1	0	0	0	4	1	0	0	4	0	3
LACTIC ACIDOSIS
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
MALNUTRITION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 38 (0.00%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 106 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
VITAMIN D DEFICIENCY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 38 (2.63%)	0 / 41 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 106 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

27 Apr 2015

- Amendment to the Phase Ib portion to be a safety run-in at the 1.8 mg/kg polatuzumab vedotin dose for each lymphoma histology. The original design for a Phase Ib dose-escalation of polatuzumab vedotin to 2.4 mg/kg was modified following the issuance of a Partial Clinical Hold at the 2.4 mg/kg dose by the U.S. Food and Drug Administration in September 2014. - Adoption of the new Lugano 2014 response criteria (Cheson et al. 2014) for NHL (which were published after finalization the first protocol), for evaluating CR by PET at the primary response assessment by IRC.

14 Sep 2015

Modification of the Lugano 2014 response criteria; Update to eligibility criteria; Inclusion of gastrointestinal perforations as an identified risk associated with obinutuzumab treatment; Updates to the guidelines for monitoring of hepatitis B reactivation for patients with occult or prior hepatitis B virus infection

11 Jul 2017

The primary purpose of this amendment was to include second malignancies as a Clinical Study Report: polatuzumab vedotin - F. Hoffmann-La Roche Ltd Protocol GO29365 Report Number 1078954 108 AESI/non-serious expedited AE requiring expedited reporting, and to require indefinite reporting of second malignancies (even if the study has ended) for patients enrolled in the obinutuzumab containing cohorts (pola+BG).

16 Nov 2017

The primary purpose of this amendment was to add an additional cohort of 2030 patients (Arm G) with R/R DLBCL who will receive a new lyophilized formulation of polatuzumab vedotin (140 mg/vial) in combination with BR, in order to gain clinical experience with this combination in R/R DLBCL in terms of PK and safety. Additionally, protocol v5 introduced the analysis of PFS and DOR by IRC for the DLBCL cohorts as requested by the U.S. FDA

31 May 2018

The primary purpose of this amendment was the expansion of Arm G, adding 10 patients with R/R DLBCL with one prior line of therapy (i.e., second line [2L]) to evaluate the efficacy of polatuzumab vedotin (lyophilized) in combination with BR. Protocol v6 also added the analysis of IRC assessed best overall response for the DLBCL cohorts.

23 Mar 2020

Updated reporting requirements for cases of second malignancies to be reported indefinitely for all enrolled subjects ; Updated reporting requirements for cases of accidental overdose or medication error, which are no longer required to be reported within 24 hours after learning of the event; Safety language

07 Oct 2020

The primary purpose of this amendment was to add a new arm (Arm H) to the Phase II lyophilized formulation Cohort to enroll approximately 60 patients with R/R DLBCL who were to receive the 140- mg/vial lyophilized formulation of polatuzumab vedotin in addition to BR in order to gain supportive clinical experience with the combination of polatuzumab vedotin (lyophilized formulation) with BR.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination with Rituximab (R) Or Obinutuzumab (G) Plus Bendamustine (B) In Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase Ib: Percentage of Participants with Adverse Events (AEs)

Primary: Phase Ib: Percentage of Participants with Adverse Events (AEs)

Primary: Arm G+H (Phase II NF Cohort): Percentage of Participants with AEs

Primary: Arm G+H (Phase II NF Cohort): Percentage of Participants with AEs

Primary: Cohort 1a (Phase Ib): Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin

Primary: Cohort 1a (Phase Ib): Percentage of Participants with Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin

Primary: Cohort 1b (Phase Ib): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Primary: Cohort 1b (Phase Ib): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Primary: Arms G+H: (Phase II NF Cohorts): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)

Primary: Arms G+H: (Phase II NF Cohorts): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)

Primary: Phase II Randomised and NF Cohorts: Percentage of Participants with Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)

Primary: Phase II Randomised and NF Cohorts: Percentage of Participants with Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)

Primary: Arm H (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

Primary: Arm H (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

Primary: Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)

Primary: Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)

Secondary: Phase II: Percentage of Participants with AEs

Secondary: Phase II: Percentage of Participants with AEs

Secondary: Arms A and C (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin

Secondary: Arms A and C (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin

Secondary: Arms E and F (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Secondary: Arms E and F (Phase II): Percentage of Participants with Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Secondary: Phase II: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator

Secondary: Phase II: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator

Secondary: Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

Secondary: Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants with CR at PRA Based on PET-CT as Determined by the IRC

Secondary: Phase II: Percentage of Participants with Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator

Secondary: Phase II: Percentage of Participants with Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator

Secondary: Phase II: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC

Secondary: Phase II: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC

Secondary: Phase II: Percentage of Participants with CR at PRA Based on CT only as Determined by Investigator

Secondary: Phase II: Percentage of Participants with CR at PRA Based on CT only as Determined by Investigator

Secondary: Phase II: Percentage of Participants with CR at PRA Based on CT Only as Determined by IRC

Secondary: Phase II: Percentage of Participants with CR at PRA Based on CT Only as Determined by IRC

Secondary: Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by Investigator

Secondary: Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by Investigator

Secondary: Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by IRC

Secondary: Phase II: Percentage of Participants with OR at PRA Based on CT only as Determined by IRC

Secondary: Phase II: Percentage of Participants with Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator

Secondary: Phase II: Percentage of Participants with Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator

Secondary: DLBCL Cohorts: Percentage of Participants with BOR based PET-CT or CT Only as Determined by IRC

Secondary: DLBCL Cohorts: Percentage of Participants with BOR based PET-CT or CT Only as Determined by IRC

Secondary: DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator

Secondary: DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator

Secondary: DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC

Secondary: DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC

Secondary: DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator

Secondary: DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator

Secondary: DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC

Secondary: DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC

Secondary: Phase II NF Cohort: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator

Secondary: Phase II NF Cohort: Percentage of Participants with CR at PRA Based on PET-CT as Determined by the Investigator

Secondary: Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by Investigator

Secondary: Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by Investigator

Secondary: Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC

Secondary: Phase II NF Cohort: Percentage of Participants with OR at PRA Based on PET-CT as Determined by IRC

Secondary: Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the IRC

Secondary: Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the IRC

Secondary: Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the Investigator

Secondary: Phase II NF Cohorts: Percentage of Participants with BOR Based on PET-CT or CT Only as Determined by the Investigator

Secondary: Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator

Secondary: Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator

Secondary: Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

Secondary: Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

Clinical Trial Results:
A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination with Rituximab (R) Or Obinutuzumab (G) Plus Bendamustine (B) In Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma