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Clinical Trial Results:
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Summary
EudraCT number	2015-001999-22
Trial protocol	ES
Global end of trial date	15 Dec 2021

Results information
Results version number	v2(current)
This version publication date	09 Apr 2024
First version publication date	18 Dec 2022
Other versions	v1
Version creation reason	Correction of full data set Align results data set with updates made to CT.gov results post NIH QA comments.

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

GO29834

ISRCTN number

US NCT number

NCT02600897

WHO universal trial number (UTN)

Sponsor organisation name

F. 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, genentech@druginfo.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

15 Dec 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of the study was to evaluate the safety, tolerability and determine the recommended phase 2 dose (RP2D) of polatuzumab vedotin (pola) and lenalidomide (Len) when given in combination with a fixed dose of obinutuzumab (G) in participants with follicular lymphoma (FL) and the RP2D of len when given in combination with a fixed dose of pola and rituximab (R) in participants with diffuse large B-cell lymphoma (DLBCL). The study also evaluated the efficacy of induction treatment with G + Pola +Len in relapsed or refractory (R/R) FL and R+ Pola + Len in R/R DLBCL.

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

24 Mar 2016

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 57

Country: Number of subjects enrolled

United Kingdom: 29

Country: Number of subjects enrolled

United States: 28

Worldwide total number of subjects

114

EEA total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 114 participants with R/R FL or DLBCL were enrolled in this study at 28 investigative sites in Spain, United Kingdom and United States from 24 March 2016 to 15 December 2021. The study consisted of two phases: dose-escalation and dose-expansion phase. All eligible participants in both phases received induction & post-induction therapy.

Screening details

Participants were enrolled in Phase Ib & Phase II study to receive polatuzumab vedotin + lenalidomide & fixed doses of rituximab/obinutuzumab. Of the 114 enrolled participants, 113 participants received at least one dose of the study drug & their intended treatment. 1 participant withdrew consent prior to receiving any study 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

Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL

Arm description

Participants with FL received lenalidomide, 10 milligrams (mg) capsules orally once daily (QD) on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as intravenous (IV) infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 milligrams per kilogram (mg/kg), IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules 10 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by maintenance treatment (only for R/R FL participants with CR, PR or SD) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 12 months.

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received polatuzumab vedotin via IV infusion at doses of 1.4 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion administered on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by maintenance treatment (only for participants with CR, PR or SD) at a dose of 1000 mg via IV infusion on Day 1 of every other month until disease progression or unacceptable toxicity for up to 24 months.

Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL

Arm description

Participants with FL received lenalidomide, 10 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules 10 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by maintenance treatment (only for R/R FL participants with CR, PR or SD) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 12 months.

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received polatuzumab vedotin via IV infusion at doses of 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received a fixed dose of obinutuzumab, 1000 mg via IV infusion administered on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by maintenance treatment (only for participants with CR, PR or SD) at a dose of 1000 mg via IV infusion on Day 1 of every other month until disease progression or unacceptable toxicity for up to 24 months.

Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL

Arm description

Participants with FL received lenalidomide, 15 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules 15 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by maintenance treatment (only for R/R FL participants with CR, PR or SD) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 12 months.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received polatuzumab vedotin via IV infusion at doses of 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL

Arm description

Participants with FL received lenalidomide, 20 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules, 20 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by maintenance treatment (only for R/R FL participants with CR, PR or SD) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 12 months.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received polatuzumab vedotin via IV infusion at doses of 1.4 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL

Arm description

Participants with DLBCL received lenalidomide, 10 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 milligrams per square meter (mg/m^2), as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months. During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m^2 IV on Day 1 of every other month for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

All participants received lenalidomide oral capsules 10 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by consolidation treatment (only for participants with CR or PR) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 6 months.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received a fixed dose of rituximab, 375 mg/m^2 via intravenous (IV) infusion on Day 1 of Cycle 1 to 6 followed by consolidation treatment (for participants with CR or PR) at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month until disease progression or unacceptable toxicity for up to 6 months.

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R DLBCL received polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL

Arm description

Participants with DLBCL received lenalidomide, 15 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months. During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m^2 IV on Day 1 of every other month for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

All participants received lenalidomide oral capsules 15 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by consolidation treatment (only for participants with CR or PR) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 6 months.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received a fixed dose of rituximab, 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 to 6 followed by consolidation treatment (for participants with CR or PR) at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month until disease progression or unacceptable toxicity for up to 6 months.

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R DLBCL received polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL

Arm description

Participants with DLBCL received lenalidomide, 20 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 mg/m^2, as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months. During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m^2 IV on Day 1 of every other month for up to 6 months.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules 20 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by consolidation treatment (only for participants with CR or PR) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 6 months.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R DLBCL received polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL

Arm description

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules, 20 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in expansion phase followed by maintenance treatment (only for participants with CR or PR) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 12 months.

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received polatuzumab vedotin via IV infusion at dose 1.4 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R FL received a fixed dose of obinutuzumab, 1000 mg via IV infusion administered on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by maintenance treatment (only for participants with CR, PR or SD) at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months until disease progression or unacceptable toxicity.

Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL

Arm description

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received lenalidomide oral capsules, 20 mg on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in expansion phase followed by consolidation treatment (only for participants with CR or PR) at a dose of 10 mg once daily on Days 1 to 21 of each month (1 month=28 days). Post-induction lenalidomide was continued until disease progression or unacceptable toxicity for up to 6 months.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Polatuzumab Vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants with R/R DLBCL received polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Number of subjects in period 1	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Started	3	4	3	6	3	5	10	40	40
Intent-to-Treat Population	3	4	3	6	3	5	10	40	40
Safety-evaluable Population	3	4	3	6	3	5	10	40	39
Pharmacokinetic-evaluable Population	3	4	3	6	3	5	10	40	39
Immunogenicity-evaluable Population	3	4	3	6	3	5	10	39	38
Completed	1	2	2	4	0	3	0	28	17
Not completed	2	2	1	2	3	2	10	12	23
Adverse event, serious fatal	1	2	1	2	3	2	10	7	20
Consent withdrawn by subject	-	-	-	-	-	-	-	4	2
Reason Not Specified	-	-	-	-	-	-	-	-	1
Lost to follow-up	1	-	-	-	-	-	-	1	-

Baseline characteristics

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Reporting group title

Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL

Reporting group description

Reporting group values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL	Total
Number of subjects	3	4	3	6	3	5	10	40	40	114
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	61.3 ( 6.1 )	72.5 ( 8.1 )	56.0 ( 3.5 )	58.3 ( 12.0 )	59.7 ( 6.5 )	62.0 ( 14.9 )	61.4 ( 14.2 )	61.6 ( 11.2 )	68.4 ( 12.8 )	-
Sex: Female, Male
Units:
Female	2	3	2	4	0	1	4	12	14	42
Male	1	1	1	2	3	4	6	28	26	72
Ethnicity
Units: Subjects
Hispanic or Latino	0	0	0	0	0	1	3	4	4	12
Not Hispanic or Latino	3	4	2	6	3	4	7	34	34	97
Not Stated	0	0	1	0	0	0	0	2	1	4
Unknown	0	0	0	0	0	0	0	0	1	1
Race
Units: Subjects
Asian	0	0	0	0	0	0	0	1	1	2
White	3	4	3	6	3	5	10	36	38	108
Unknown or Not Reported	0	0	0	0	0	0	0	3	1	4
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0	0
More than one race	0	0	0	0	0	0	0	0	0	0

End points

Top of page

Reporting group title

Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL

Reporting group description

Reporting group title

Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL

Reporting group description

Primary: Percentage of Participants with Dose-Limiting Toxicities (DLTs)

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End point title

Percentage of Participants with Dose-Limiting Toxicities (DLTs) ^[1] ^[2]

End point description

A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of > 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase > 3 x baseline and an increase in direct bilirubin > 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). The safety-evaluable population included all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase

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: No descriptive statistics were planned 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: No descriptive statistics were planned for this endpoint.

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	5	10
Units: percentage of participants
number (not applicable)	0.0	50.0	0.0	0.0	0.0	0.0	0.0

No statistical analyses for this end point

Primary: Percentage of Participants with Adverse Events (AEs)

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End point title

Percentage of Participants with Adverse Events (AEs) ^[3]

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. Percentages have been rounded off to the first decimal point. The safety-evaluable population included all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

From study start up to end of study (Up to a maximum of 69 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: No descriptive statistics were planned for this endpoint.

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	5	10	40	39
Units: percentage of participants
number (not applicable)	100.0	100.0	100.0	100.0	100.0	100.0	100.0	100.0	97.4

No statistical analyses for this end point

Primary: Percentage of Participants with Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans

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End point title

Percentage of Participants with Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans ^[4] ^[5]

End point description

CR at EOI was assessed by IRC according to Modified Lugano Response Criteria. Per MLRC CR based on PET-CT was defined as complete metabolic response in lymph nodes & extralymphatic sites with score of 1, 2, 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 &/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry negative. Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL)

End point type

Primary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[4] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.
[5] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	10	40	39
Units: percentage of participants
number (confidence interval 90%)	66.7 (27.13 to 93.72)	0.0 (0.0 to 25.89)	60.0 (45.78 to 73.06)	38.5 (25.41 to 52.89)

No statistical analyses for this end point

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans

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End point title

Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans ^[6]

End point description

CR at EOI was assessed by investigator according to Modified Lugano Response Criteria. Per MLRC CR based on PET-CT was = complete metabolic response in lymph nodes & extralymphatic sites with score of 1, 2, 3 with or without residual mass, on 5-point scale where 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 fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry negative. Percentages have been rounded off to the first decimal point. Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs at RP2D.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	10	40	39
Units: percentage of participants
number (confidence interval 90%)	66.7 (27.13 to 93.72)	0.0 (0.0 to 25.89)	60.0 (45.78 to 73.06)	33.3 (20.97 to 47.69)

No statistical analyses for this end point

Secondary: Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

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End point title

Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone ^[7]

End point description

CR at EOI was determined by IRC 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 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs at RP2D. (1.4 mg Pola + 20 mg L for FL; 20 mg L for DLBCL) . Number of Subjects Analyzed=number

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[7] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	8	35	32
Units: percentage of participants
number (confidence interval 90%)	16.7 (0.85 to 58.18)	0.0 (0.0 to 31.23)	31.4 (18.73 to 46.61)	12.5 (4.38 to 26.36)

No statistical analyses for this end point

Secondary: Percentage of Participants with CR at EOI, Determined by Investigator on the Basis of CT Scans Alone

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End point title

Percentage of Participants with CR at EOI, Determined by Investigator on the Basis of CT Scans Alone ^[8]

End point description

CR at EOI was determined by Investigator 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 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off up to the second decimal point.Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs at RP2D.1.4 mg Pola + 20 mg L for FL; 20 mg L for DLBCL). Number of Subjects Analyzed=number of subject with data available for analysis.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	9	37	32
Units: percentage of participants
number (confidence interval 90%)	16.7 (0.85 to 58.18)	0.0 (0.0 to 28.31)	29.7 (17.65 to 44.38)	28.1 (15.53 to 43.94)

No statistical analyses for this end point

Secondary: Percentage of Participants with Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans

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End point title

Percentage of Participants with Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans ^[9]

End point description

OR was defined as %of participants withCR/PR as assessed by IRC according toMLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes&ELS with score=1/2/3 with or without residual mass on 5PSwhere 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 new lesions&no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate IHC negative. PR based on PET-CT=partial MR in lymph nodes&ELS with score=4/5 with reduced uptake compared with baseline&residual masses of any size at interim,residual uptake > uptake in normal bone marrow but reduced compared with baseline. Efficacy-evaluable population=all participants who received at least one dose of any component of combination. Participants with FL & DLBCL who received pola &/or L at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[9] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D..

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	10	40	39
Units: percentage of participants
number (confidence interval 90%)	100.0 (60.70 to 100.0)	10.0 (0.51 to 39.42)	72.50 (58.61 to 83.75)	46.20 (32.35 to 60.42)

No statistical analyses for this end point

Secondary: Percentage of Participants with Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans

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End point title

Percentage of Participants with Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans ^[10]

End point description

OR=%of participants withCR/PR as assessed by investigator according toMLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes&ELS with score=1/2/3 with or without residual mass on 5PSwhere 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 new lesions&no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate IHC negative. PR based on PET-CT=partial MR in lymph nodes&ELS with score=4/5 with reduced uptake compared with baseline&residual masses of any size at interim,residual uptake > uptake in normal bone marrow but reduced compared with baseline. Efficacy-evaluable population=all participants who received at least one dose of any component of combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion arms & n dose-escalation arms who received drugs at RP2D.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	10	40	39
Units: percentage of participants
number (confidence interval 90%)	100.0 (60.70 to 100.0)	10.0 (0.51 to 39.42)	80.0 (66.80 to 89.64)	46.20 (32.35 to 60.42)

No statistical analyses for this end point

Secondary: Percentage of Participants with Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone

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End point title

Percentage of Participants with Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone ^[11]

End point description

OR=% of participants with CR or PR as assessed by IRC based on MLRC. Per MLRC CR based on CT=complete radiologic response in lymph nodes & ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi & 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 lymph nodes & ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes & 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. Percentages have been rounded off to the first decimal point. Efficacy-evaluable population=all participants who received at least one dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs atRP2D

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[11] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D..

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	8	35	32
Units: percentage of participants
number (confidence interval 90%)	100.0 (60.70 to 100.0)	12.5 (0.64 to 47.07)	91.4 (79.31 to 97.62)	53.1 (37.34 to 68.46)

No statistical analyses for this end point

Secondary: Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone

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End point title

Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone ^[12]

End point description

OR = %participants with CR/PR as assessed by investigator based on MLRC. Per MLRC CR based on CT = complete radiologic response in lymph nodes&ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi & 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 lymph nodes & ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes & 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. Values have been rounded off to the nearest whole number. Efficacy-evaluable population=all participants who received at least one dose of any component of the combination. As pre-specified in the protocol, data was collected & analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs at RP2D.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Notes
[12] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	9	37	32
Units: percentage of participants
number (confidence interval 90%)	100.0 (60.70 to 100.0)	11.1 (0.57 to 42.91)	89.2 (76.95 to 96.22)	59.4 (43.35 to 74.03)

No statistical analyses for this end point

Secondary: Percentage of Participants with Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone

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End point title

Percentage of Participants with Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone ^[13]

End point description

BOR=CR/PR per CT per MLRC. Per MLRC, CR based on CT = complete radiologic response in lymph nodes & ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi & 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 lymph nodes & ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes & 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. Efficacy-evaluable population=all participants who received at least one dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms & those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL).

End point type

Secondary

End point timeframe

Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)

Notes
[13] - 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: Endpoint is applicable only for dose escalation arms and dose expansion arms which received the study drugs at RP2D.

End point values	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	6	10	40	39
Units: percentage of participants
number (confidence interval 90%)	100.0 (60.70 to 100.0)	50.0 (22.24 to 77.76)	90.0 (78.56 to 96.51)	79.5 (66.02 to 89.36)

No statistical analyses for this end point

Secondary: Observed Serum Obinutuzumab Concentration

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End point title

Observed Serum Obinutuzumab Concentration ^[14]

End point description

The pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one suitable postdose PK sample. 1 cycle = 28 days. ‘Overall Number Analyzed’ is the number of participants with data available for analysis. ‘Number Analyzed’ is the number of participants with data available for analysis at a specified timepoint. Here, 9999= data is not evaluable as the samples were below lower limit of quantification (BLLQ); 99999= Since low number of participants were analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint; 9999999=Values were lower than reportable (LTR) for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose;Day 1 of Maintenance Months 1,7, 13, 19; Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose(up to approximately 69 months)

Notes
[14] - 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: Endpoint is applicable only for obinutuzumab arms.

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL
Number of subjects analysed	3	4	3	6	38
Units: micrograms per milliliter (μg/mL)
geometric mean (geometric coefficient of variation)
Induction Cycle 1 Day 1 / Predose (n=3,4,2,6,37)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Induction Cycle 1 Day 1 / 30 mins(n=3,3,3,4,35)	394 ( 22.1 )	358 ( 20.5 )	351 ( 15.2 )	333 ( 70.0 )	182 ( 206.7 )
Induction Cycle 2 Day 1 / Predose(n=3,3,3,4,36)	451 ( 23.5 )	372 ( 37.0 )	386 ( 4.6 )	481 ( 23.1 )	312 ( 40.8 )
Induction Cycle 2 Day 1 / 30 mins(n=3,3,3,5,36)	830 ( 38.3 )	749 ( 17.2 )	695 ( 14.3 )	667 ( 77.5 )	588 ( 41.4 )
Induction Cycle 4 Day 1 / Predose(n=3,2,2,4,34)	354 ( 15.0 )	321 ( 43.6 )	344 ( 13.4 )	405 ( 24.9 )	270 ( 41.8 )
Induction Cycle 4 Day 1 / 30 mins(n=1,2,2,5,33)	103 ( 99999 )	644 ( 42.8 )	653 ( 20.6 )	742 ( 27.8 )	547 ( 37.1 )
Induction Cycle 6 Day 1 / Predose(n=3,1,2,5,34)	255 ( 36.6 )	504 ( 99999 )	327 ( 5.8 )	384 ( 52.2 )	255 ( 49.0 )
Induction Cycle 6 Day 1 / 30 mins(n=3,1,2,5,33)	730 ( 15.5 )	804 ( 99999 )	1.18 ( 9999999 )	751 ( 35.3 )	543 ( 36.2 )
EOI / Predose(n=3,0,0,0,0)	108 ( 32.6 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )
Maintenance Month 1 / Predose(n=2,1,0,4,27)	231 ( 19.1 )	381 ( 99999 )	999999 ( 999999 )	230 ( 87.4 )	176 ( 60.1 )
Maintenance Month 7 / Predose(n=1,1,1,3,21)	128 ( 99999 )	212 ( 99999 )	229 ( 99999 )	125 ( 143.7 )	135 ( 64.3 )
Maintenance Month 13 / Predose(n=0,1,1,3,18)	999999 ( 999999 )	142 ( 99999 )	269 ( 99999 )	134 ( 105.3 )	150 ( 70.7 )
Maintenance Month 19 / Predose(n=0,1,1,2,15)	999999 ( 999999 )	354 ( 99999 )	204 ( 99999 )	154 ( 144.1 )	165 ( 59.5 )
Study Drug Discontinuation(n=0,1,0,1,10)	999999 ( 999999 )	46.4 ( 99999 )	999999 ( 999999 )	17.3 ( 99999 )	87.5 ( 588.7 )
Day 120 Post Last Dose(n=1,0,0,0,7)	29.1 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	44.5 ( 806.5 )
1 Year Post Last Dose(n=0,0,1,0,7)	999999 ( 999999 )	999999 ( 999999 )	0.377 ( 99999 )	999999 ( 999999 )	0.340 ( 955.9 )
Unscheduled / Predose(n=0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	561 ( 99999 )

No statistical analyses for this end point

Secondary: Observed Serum Rituximab Concentration

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End point title

Observed Serum Rituximab Concentration ^[15]

End point description

End point type

Secondary

End point timeframe

Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)

Notes
[15] - 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: Endpoint is applicable only for rituximab arms.

End point values	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	5	10	37
Units: μg/mL
geometric mean (geometric coefficient of variation)
Induction Cycle 1 Day 1 / Predose(n=2,5,10,36)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Induction Cycle 1 Day 1 / 30 mins(n=2,4,9,36)	151 ( 42.9 )	203 ( 28.1 )	175 ( 18.7 )	174 ( 45.4 )
Induction Cycle 2 Day 1 / Predose(n=3,3,7,34)	25.6 ( 78.0 )	33.3 ( 43.7 )	31.7 ( 26.2 )	26.4 ( 73.4 )
Induction Cycle 2 Day 1 / 30 mins(n=1,1,1,32)	133 ( 99999 )	172 ( 99999 )	222 ( 99999 )	194 ( 36.4 )
Induction Cycle 4 Day 1 / Predose(n=1,2,4,27)	20.4 ( 99999 )	74.6 ( 33.8 )	53.1 ( 43.7 )	58.3 ( 44.4 )
Induction Cycle 4 Day 1 / 30 mins(n=1,2,4,26)	159 ( 99999 )	224 ( 5.7 )	220 ( 16.2 )	228 ( 36.6 )
Induction Cycle 6 Day 1 / Predose(n=1,3,2,19)	15.3 ( 99999 )	79.5 ( 42.3 )	74.7 ( 22.1 )	68.9 ( 60.6 )
Induction Cycle 6 Day 1 / 30 mins(n=1,2,2,19)	135 ( 99999 )	250 ( 7.6 )	233 ( 1.8 )	256 ( 26.4 )

No statistical analyses for this end point

Secondary: Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody

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End point title

Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody

End point description

The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one suitable PK samples. ‘Overall Number Analyzed’ is the number of participants with data available for analysis. ‘Number Analyzed’ is the number of participants with data available for analysis at a specified timepoint. C=cycle D=Day. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since low number of participants were analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint. 9999999= Since more than one-third values were less than reportable, the geometric coefficient of variation was not calculated; 9999999=Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	4	7	37	37
Units: μg/mL
geometric mean (geometric coefficient of variation)
Induction C1D1/ Predose(n=3,4,2,6,3,4,7,36,37)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Induction C2D1/ Predose(n=3,3,3,6,3,3,7,37,35)	1.47 ( 16.2 )	2.01 ( 51.1 )	0.200 ( 958.3 )	0.622 ( 152.8 )	1.57 ( 62.9 )	1.61 ( 59.8 )	1.47 ( 26.2 )	0.339 ( 391.8 )	1.35 ( 122.0 )
Induction C4D1/ Predose(n=3,2,2,5,1,3,4,35,26)	1.83 ( 51.7 )	4.45 ( 20.5 )	2.57 ( 30.5 )	2.12 ( 69.0 )	0.900 ( 99999 )	2.96 ( 44.4 )	3.10 ( 43.6 )	2.31 ( 48.5 )	3.42 ( 46.1 )
Study Drug Discontinuation(n=3,1,0,2,1,1,3,11,18)	0.106 ( 209.1 )	0.170 ( 99999 )	999999 ( 999999 )	0.0903 ( 9999999 )	1.50 ( 99999 )	6.16 ( 99999 )	3.25 ( 49.7 )	0.175 ( 9999999 )	0.455 ( 448.4 )
Day 120 Post Last Dose(n=1,0,0,0,0,1,1,9,9)	0.0661 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.208 ( 99999 )	0.107 ( 99999 )	0.0365 ( 9999999 )	0.0666 ( 9999999 )
1 Year Post Last Dose(n=1,0,1,0,0,0,0,7,9)	0.0250 ( 99999 )	999999 ( 999999 )	0.0250 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.0357 ( 9999999 )	0.0250 ( 9999999 )
Unscheduled / Predose(n=0,0,0,0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	2.59 ( 99999 )

No statistical analyses for this end point

Secondary: Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)

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End point title

Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)

End point description

The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one suitable PK samples. ‘Overall Number Analyzed’ is the number of participants with data available for analysis. ‘Number Analyzed’ is the number of participants with data available for analysis at a specified timepoint. C=Cycle D=Day. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since low number of participants were analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint; 9999999=Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	5	10	40	39
Units: nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)
Induction C1D1 / Predose(n=3,4,2,6,3,5,10,38,38)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Induction C1D1 / 30 mins(n=2,4,3,6,3,5,10,34,36)	580 ( 41.6 )	660 ( 24.7 )	476 ( 16.0 )	432 ( 27.9 )	568 ( 27.7 )	106 ( 60902.6 )	513 ( 73.5 )	333 ( 267.2 )	522 ( 323.0 )
Induction C1D8 (n=3,3,3,5,3,5,7,35,36)	50.2 ( 7.3 )	80.0 ( 17.6 )	11.4 ( 232.2 )	27.7 ( 69.2 )	58.9 ( 44.4 )	52.0 ( 36.3 )	43.9 ( 96.4 )	11.9 ( 799.0 )	56.6 ( 90.2 )
Induction C1D15 (n=3,3,3,5,2,5,7,33,33)	17.3 ( 5.5 )	24.7 ( 13.8 )	2.50 ( 483.1 )	6.73 ( 118.8 )	22.3 ( 31.2 )	18.3 ( 48.7 )	18.6 ( 30.5 )	5.95 ( 366.1 )	16.9 ( 118.6 )
Induction C2D1 / Predose(n=3,3,3,6,3,3,7,38,33)	4.96 ( 21.3 )	6.55 ( 58.7 )	0.961 ( 477.5 )	2.50 ( 119.8 )	7.44 ( 40.2 )	5.58 ( 77.2 )	6.12 ( 18.1 )	1.88 ( 490.2 )	5.32 ( 103.6 )
Induction C2D1 / 30 mins(n=3,3,3,6,3,3,7,36,31)	555 ( 15.8 )	623 ( 18.4 )	508 ( 22.7 )	295 ( 174.6 )	537 ( 40.3 )	568 ( 14.1 )	716 ( 16.5 )	481 ( 54.3 )	451 ( 391.7 )
Induction C4D11 / Predose(n=3,1,2,5,1,3,4,36,26)	5.34 ( 73.9 )	11.5 ( 99999 )	8.47 ( 19.5 )	7.68 ( 60.8 )	4.19 ( 99999 )	8.25 ( 59.4 )	11.7 ( 74.2 )	8.99 ( 36.7 )	11.3 ( 45.2 )
Induction C4D1 / 30 mins(n=3,1,2,5,1,3,4,36,26)	32.9 ( 101980.7 )	416 ( 87.7 )	519 ( 9.3 )	531 ( 17.6 )	371 ( 99999 )	507 ( 42.8 )	737 ( 20.8 )	492 ( 22.3 )	645 ( 107.2 )
Induction C6D1 / Predose(n=3,1,2,5,1,3,2,33,21)	7.70 ( 26.0 )	19.9 ( 99999 )	9.37 ( 42.6 )	9.70 ( 53.0 )	3.06 ( 99999 )	11.5 ( 41.6 )	15.8 ( 45.4 )	9.82 ( 40.4 )	11.8 ( 66.0 )
Study Drug Discontinuation(n=2,1,0,1,0,0,0,4,0)	0.180 ( 9999999 )	0.635 ( 99999 )	999999 ( 999999 )	0.180 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	1.71 ( 378.4 )	999999 ( 999999 )
Unscheduled / Predose(n=0,0,0,0,0,0,0,0,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	23.1 ( 62.5 )	9.78 ( 99999 )

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

End point description

The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one suitable PK samples. ‘Overall Number Analyzed’ is the number of participants with data available for analysis. ‘Number Analyzed’ is the number of participants with data available for analysis at a specified timepoint. C=Cycle D=Day. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since low number of participants were analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint. 9999999= Since more than one-third values were less than reportable, the geometric coefficient of variation was not calculated; 9999999=Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	5	10	40	39
Units: ng/mL
geometric mean (geometric coefficient of variation)
Induction C1D1 / Predose(n=3,4,2,6,3,5,10,38,38)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Induction C1D1 / 30 mins(n=2,4,3,6,3,5,10,35,36)	0.228 ( 7.8 )	0.160 ( 69.9 )	0.420 ( 100.6 )	0.233 ( 74.0 )	0.156 ( 62.1 )	0.167 ( 214.8 )	0.298 ( 198.7 )	0.347 ( 327.5 )	0.297 ( 111.1 )
Induction C1D8 (n=3,4,3,5,3,5,7,37,36)	1.15 ( 34.9 )	2.05 ( 49.7 )	2.40 ( 102.0 )	1.64 ( 135.5 )	1.89 ( 76.1 )	1.36 ( 29.6 )	3.65 ( 75.3 )	1.12 ( 227.0 )	2.56 ( 144.8 )
Induction C1D15 (n=3,3,3,6,2,5,7,33,34)	0.457 ( 56.3 )	0.459 ( 54.5 )	0.387 ( 6.0 )	0.435 ( 129.5 )	0.485 ( 204.0 )	0.456 ( 39.8 )	0.683 ( 63.3 )	0.294 ( 170.9 )	0.843 ( 125.2 )
Induction C2D1 / Predose(n=3,3,3,6,3,3,7,38,34)	0.0280 ( 9999999 )	0.0315 ( 9999999 )	0.0244 ( 9999999 )	0.0334 ( 9999999 )	0.0501 ( 149.0 )	0.0310 ( 9999999 )	0.0527 ( 102.8 )	0.0268 ( 9999999 )	0.0713 ( 125.0 )
Induction C2D1 / 30 minsn=3,3,3,6,3,3,7,36,31)	0.151 ( 68.6 )	0.138 ( 133.0 )	0.151 ( 49.8 )	0.136 ( 339.9 )	0.186 ( 51.2 )	0.123 ( 53.8 )	0.157 ( 72.5 )	0.102 ( 101.2 )	0.210 ( 77.3 )
Induction C4D1 / Predose(n=3,1,2,5,1,3,4,36,26)	0.0431 ( 99999 )	0.117 ( 99999 )	0.0672 ( 56.9 )	0.0283 ( 9999999 )	0.0180 ( 99999 )	0.0344 ( 61.0 )	0.0729 ( 11.4 )	0.0366 ( 9999999 )	0.0776 ( 101.5 )
Induction C4D1 / 30 mins(n=2,2,2,5,1,3,4,34,39)	0.0817 ( 9999999 )	0.156 ( 18.7 )	0.104 ( 7.1 )	0.0752 ( 113.2 )	0.0180 ( 99999 )	0.133 ( 50.9 )	0.208 ( 44.9 )	0.102 ( 57.7 )	0.213 ( 51.3 )
Induction C6D1 / Predose(n=3,1,2,5,1,3,2,33,21)	0.0367 ( 68.3 )	0.0929 ( 99999 )	0.0821 ( 93.8 )	0.0267 ( 9999999 )	0.0180 ( 99999 )	0.0517 ( 118.9 )	0.0405 ( 9999999 )	0.0342 ( 9999999 )	0.0852 ( 62.6 )
Study Drug Discontinuation(n=2,1,0,1,0,0,0,4,0)	0.0180 ( 9999999 )	0.0180 ( 99999 )	999999 ( 999999 )	0.0180 ( 99999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.0180 ( 9999999 )	999999 ( 999999 )
Unscheduled / Predose(n=0,0,0,0,0,0,0,1,1)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	0.180 ( 99999 )	0.0180 ( 99999 )

No statistical analyses for this end point

Secondary: Observed Plasma Lenalidomide Concentration

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End point title

Observed Plasma Lenalidomide Concentration

End point description

The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one suitable PK samples. ‘Overall Number Analyzed’ is the number of participants with data available for analysis. ‘Number Analyzed’ is the number of participants with data available for analysis at a specified timepoint. C=Cycle D=Day. Here, 9999= data is not evaluable as the samples were BLLQ; 99999= Since low number of participants were analysed, the geometric coefficient of variation was not calculated; 999999= participants were not analysed for this PK endpoint at the given timepoint; 9999999=Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	4	10	37	37
Units: ng/mL
geometric mean (geometric coefficient of variation)
Induction C1D1 / Predose(n=3,4,2,5,3,4,9,36,36)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Induction C1D1 / 2h(n=3,4,3,5,3,4,10,37,36)	118 ( 44.0 )	144 ( 30.3 )	201 ( 54.0 )	305 ( 37.1 )	25.2 ( 239.4 )	237 ( 47.4 )	197 ( 184.1 )	306 ( 43.1 )	277 ( 60.0 )
Induction C1D15 / Predose(n=3,3,2,6,2,4,7,32,31)	5.97 ( 628.0 )	0.729 ( 540.0 )	8.74 ( 277.0 )	5.20 ( 275.1 )	5.43 ( 9.1 )	2.64 ( 68.0 )	8.33 ( 112.0 )	9.99 ( 260.9 )	10.4 ( 196.4 )
Induction C1D15 / 30 min(n=3,2,2,4,2,3,7,30,30)	64.0 ( 1553.1 )	1.95 ( 9999999 )	179 ( 220.1 )	202 ( 115.6 )	12.5 ( 76.4 )	41.7 ( 546.7 )	73.3 ( 395.5 )	124 ( 300.3 )	94.5 ( 204.9 )
Induction C1D15 / 1h(n=3,3,2,5,2,3,7,33,30)	61.4 ( 1354.8 )	40.8 ( 183.1 )	189 ( 48.0 )	272 ( 48.2 )	69.9 ( 10.3 )	224 ( 76.8 )	187 ( 150.5 )	236 ( 147.7 )	245 ( 106.8 )
Induction C1D15 / 2h(n=3,3,2,5,2,3,7,33,30)	117 ( 53.2 )	93.3 ( 40.5 )	202 ( 36.0 )	200 ( 45.5 )	118 ( 22.3 )	232 ( 25.5 )	328 ( 38.2 )	305 ( 53.6 )	242 ( 297.2 )
Induction C1D15 / 4h(n=3,3,2,4,2,3,7,33,31)	96.4 ( 62.0 )	65.7 ( 46.3 )	116 ( 28.9 )	152 ( 36.9 )	79.9 ( 28.2 )	134 ( 23.6 )	245 ( 36.3 )	214 ( 41.1 )	205 ( 45.4 )
Induction C1D15 / 8h(n=3,3,2,5,2,3,7,28,30)	35.0 ( 109.1 )	29.2 ( 55.2 )	56.8 ( 57.2 )	49.8 ( 23.3 )	44.0 ( 40.2 )	57.0 ( 19.1 )	105 ( 50.9 )	103 ( 56.3 )	103 ( 67.6 )
Induction C6D1 / 2h(n=3,1,2,5,2,3,2,33,19)	124 ( 21.4 )	76.1 ( 99999 )	110 ( 35.1 )	227 ( 48.1 )	36.2 ( 9999999 )	258 ( 10.5 )	255 ( 36.5 )	237 ( 52.1 )	153 ( 515.5 )
Unscheduled / 2h(n=0,0,0,0,0,0,0,3,0)	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	199 ( 53.3 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Number of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab

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End point title

Number of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab ^[16]

End point description

The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline & at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during study period. Treatment-induced ADA = negative or missing baseline ADA result & 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 titer unit (t.u.) > baseline titer result. Immunogenicity population included all safety-evaluable participants with at least one ADA Sample. 'Overall Number Analyzed'=number of participants with data available for analysis. 'Number Analyzed' =number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Baseline up to approximately 2 years after last dose (up to approximately 69 months)

Notes
[16] - 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: Endpoint is applicable only for Obinutuzumab arms.

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL
Number of subjects analysed	3	4	2	6	38
Units: participants
Baseline prevalence of ADAs(n=3,4,2,6,38)	0	0	0	0	3
Post baseline incidence of ADAs(n=3,2,2,6,36)	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab

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End point title

Number of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab ^[17]

End point description

The number of participants with positive results for HACAs, also called ADAs against rituximab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during study period. Treatment-induced ADA = negative or missing baseline ADA result(s) & 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. > baseline titer result. Immunogenicity population included all safety-evaluable participants with at least one ADA Sample. 'Overall Number Analyzed' is the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Baseline up to approximately 2 years after last dose (up to approximately 69 months)

Notes
[17] - 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: Endpoint is applicable only for rituximab arms.

End point values	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	5	10	37
Units: participants
Baseline prevalence of ADAs(n=2,5,10,36)	0	0	0	0
Post baseline incidence of ADAs(n=3,4,7,37)	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

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End point title

Number of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

End point description

The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline & at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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 t.u. > baseline titer result. Immunogenicity population included all safety-evaluable participants with at least one ADA sample. 'Number Analyzed'=number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)

End point values	Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL	Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL
Number of subjects analysed	3	4	3	6	3	5	10	39	38
Units: participants
Baseline prevalence (n=3,4,2,6,3,5,10,38,37)	0	0	0	0	0	0	0	1	1
Post baseline incidence(n=3,4,3,6,3,4,7,38,37)	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline up to study completion/discontinuation (maximum of 69 months)

Adverse event reporting additional description

The safety-evaluable population was defined as all participants who received at least one dose of any component of the combination.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4mg Pola + 15mg L + 1000mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4mg Pola + 20mg L + 1000mg G in FL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.4mg Pola + 10mg L + 1000mg G in FL

Reporting group description

Participants with FL received lenalidomide, 10 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months.

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Expansion Phase: 1.4mg Pola + 20mg L + 1000mg G in FL

Reporting group description

Reporting group title

Expansion Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL

Reporting group description

Reporting group title

Dose-escalation Phase: 1.8mg Pola + 10mg L + 1000mg G in FL

Reporting group description

Serious adverse events	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.4mg Pola + 15mg L + 1000mg G in FL	Dose-escalation Phase: 1.4mg Pola + 20mg L + 1000mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.4mg Pola + 10mg L + 1000mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4mg Pola + 20mg L + 1000mg G in FL	Expansion Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 1000mg G in FL
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 5 (0.00%)	2 / 3 (66.67%)	3 / 6 (50.00%)	0 / 3 (0.00%)	3 / 3 (100.00%)	4 / 10 (40.00%)	26 / 40 (65.00%)	19 / 39 (48.72%)	2 / 4 (50.00%)
number of deaths (all causes)	2	1	2	3	1	10	7	20	2
number of deaths resulting from adverse events	0	0	0	0	0	0	1	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TUMOUR FLARE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1	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
LUNG NEOPLASM MALIGNANT
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CANCER PAIN
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
PYREXIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1	0 / 0	1 / 2	1 / 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
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DYSPNOEA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMOTHORAX
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
CONFUSIONAL STATE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
C-REACTIVE PROTEIN INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
HIP FRACTURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ANKLE FRACTURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THORACIC VERTEBRAL FRACTURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFUSION RELATED REACTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	1 / 1	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
FALL
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
UPPER LIMB FRACTURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FEMUR FRACTURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
PERICARDITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ACUTE MYOCARDIAL INFARCTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ACUTE CORONARY SYNDROME
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	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
CARDIAC FAILURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
ENCEPHALOPATHY
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BRAIN STEM STROKE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
SEIZURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ISCHAEMIC STROKE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Blood and lymphatic system disorders
NEUTROPENIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	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
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	2 / 4	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
THROMBOCYTOPENIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	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
Eye disorders
VISION BLURRED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
GASTRIC HAEMORRHAGE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
COLITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LIP SWELLING
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
RASH
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
STEVENS-JOHNSON SYNDROME
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	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 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
RENAL FAILURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
URINARY RETENTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
HYPOTHYROIDISM
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
BRONCHIOLITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INJECTION SITE INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	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 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 3	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
LUNG ABSCESS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIC SEPSIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	2 / 2	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
UROSEPSIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 4	0 / 2	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
COVID-19
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 1	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
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 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
CELLULITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (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
deaths causally related to treatment / all	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 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
SEPTIC SHOCK
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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
EPIDIDYMITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
HYPERCALCAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
DEHYDRATION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (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
deaths causally related to treatment / all	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 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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

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

Non-serious adverse events	Dose-escalation Phase: 1.8mg Pola + 15mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.4mg Pola + 15mg L + 1000mg G in FL	Dose-escalation Phase: 1.4mg Pola + 20mg L + 1000mg G in FL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.4mg Pola + 10mg L + 1000mg G in FL	Dose-escalation Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Expansion Phase: 1.4mg Pola + 20mg L + 1000mg G in FL	Expansion Phase: 1.8mg Pola + 20mg L + 375mg R in DLBCL	Dose-escalation Phase: 1.8mg Pola + 10mg L + 1000mg G in FL
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 5 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	9 / 10 (90.00%)	40 / 40 (100.00%)	37 / 39 (94.87%)	4 / 4 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR FLARE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	2	1	1
SQUAMOUS CELL CARCINOMA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Vascular disorders
FLUSHING
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
HYPERTENSION
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
General disorders and administration site conditions
CHILLS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	3 / 40 (7.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	5	2	0
PYREXIA
subjects affected / exposed	1 / 5 (20.00%)	2 / 3 (66.67%)	3 / 6 (50.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	1 / 10 (10.00%)	13 / 40 (32.50%)	5 / 39 (12.82%)	0 / 4 (0.00%)
occurrences all number	1	6	3	1	3	2	17	5	0
PAIN
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0
FATIGUE
subjects affected / exposed	1 / 5 (20.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	11 / 40 (27.50%)	6 / 39 (15.38%)	0 / 4 (0.00%)
occurrences all number	1	2	0	0	2	0	11	6	0
INFLUENZA LIKE ILLNESS
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	4 / 40 (10.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	1	0	4	0	0
ASTHENIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 10 (20.00%)	7 / 40 (17.50%)	6 / 39 (15.38%)	2 / 4 (50.00%)
occurrences all number	0	1	1	1	0	2	12	6	2
FEELING ABNORMAL
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
GAIT DISTURBANCE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
OEDEMA PERIPHERAL
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	4 / 40 (10.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	2	4	2	0
PERIPHERAL SWELLING
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	4	0
Immune system disorders
HYPOGAMMAGLOBULINAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
CYTOKINE RELEASE SYNDROME
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0
Reproductive system and breast disorders
VULVOVAGINAL DRYNESS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0	0
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	2	2	0
RHINORRHOEA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0	2	1	0
PLEURAL EFFUSION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	2	1	0
DYSPNOEA
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	5 / 40 (12.50%)	1 / 39 (2.56%)	1 / 4 (25.00%)
occurrences all number	2	0	0	0	0	1	5	1	1
EPISTAXIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	12	0	0
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	4	1	0
RHINITIS ALLERGIC
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
UPPER-AIRWAY COUGH SYNDROME
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
COUGH
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	10 / 40 (25.00%)	5 / 39 (12.82%)	0 / 4 (0.00%)
occurrences all number	1	1	7	0	1	1	11	5	0
Psychiatric disorders
DEPRESSION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0	0
INSOMNIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	2	1	0
Investigations
BLOOD LACTATE DEHYDROGENASE INCREASED
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	3	0	0	0	0	0	5	2	0
BLOOD CREATININE INCREASED
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	5 / 40 (12.50%)	3 / 39 (7.69%)	2 / 4 (50.00%)
occurrences all number	1	0	1	0	0	0	10	4	2
BLOOD LACTATE DEHYDROGENASE DECREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
CREATININE RENAL CLEARANCE DECREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	5 / 40 (12.50%)	4 / 39 (10.26%)	0 / 4 (0.00%)
occurrences all number	4	1	2	0	0	2	7	8	0
CREATININE RENAL CLEARANCE INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
BLOOD GLUCOSE INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0	12	5	0
WEIGHT DECREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	2 / 5 (40.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	8 / 40 (20.00%)	5 / 39 (12.82%)	1 / 4 (25.00%)
occurrences all number	5	1	2	0	0	1	11	8	1
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	5 / 40 (12.50%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	2	0	1	0	0	2	10	4	0
CARDIAC STRESS TEST ABNORMAL
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	4 / 40 (10.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	2	6	0	0
LIPASE INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	0	1	1	1
IMMUNOGLOBULINS DECREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
TRANSAMINASES INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
C-REACTIVE PROTEIN INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 10 (20.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	2	3	2	0
AMYLASE INCREASED
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	0	0	0	1
Injury, poisoning and procedural complications
MUSCLE STRAIN
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
INFUSION RELATED REACTION
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	17 / 40 (42.50%)	2 / 39 (5.13%)	1 / 4 (25.00%)
occurrences all number	1	0	3	1	0	0	19	2	1
FALL
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
CONTUSION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
LEFT VENTRICULAR DYSFUNCTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Nervous system disorders
NEURALGIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
BURNING SENSATION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
RESTING TREMOR
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
DYSGEUSIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0
HEADACHE
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	3 / 40 (7.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	2	1	0	1	0	3	3	0
SYNCOPE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
PARAESTHESIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	1 / 39 (2.56%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	0	4	1	1
PERIPHERAL MOTOR NEUROPATHY
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0
DIZZINESS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	5 / 40 (12.50%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	7	4	0
HEAD TITUBATION
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
NEUROPATHY PERIPHERAL
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	3 / 40 (7.50%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	2	3	3	0
Blood and lymphatic system disorders
LYMPHOPENIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	3	0	0
NEUTROPHILIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	5	1	0
NEUTROPENIA
subjects affected / exposed	3 / 5 (60.00%)	1 / 3 (33.33%)	6 / 6 (100.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	7 / 10 (70.00%)	26 / 40 (65.00%)	25 / 39 (64.10%)	2 / 4 (50.00%)
occurrences all number	7	8	18	7	2	15	117	62	9
ANAEMIA
subjects affected / exposed	2 / 5 (40.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	5 / 10 (50.00%)	18 / 40 (45.00%)	14 / 39 (35.90%)	0 / 4 (0.00%)
occurrences all number	3	2	5	1	1	5	29	22	0
THROMBOCYTOPENIA
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	5 / 6 (83.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 10 (20.00%)	22 / 40 (55.00%)	10 / 39 (25.64%)	2 / 4 (50.00%)
occurrences all number	6	3	10	4	0	2	50	18	2
LEUKOPENIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	4	1	0
Ear and labyrinth disorders
VERTIGO
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
TYMPANIC MEMBRANE PERFORATION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Eye disorders
OCULAR HYPERAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
VISION BLURRED
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	3	0	0
DRY EYE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0
PERIORBITAL OEDEMA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Gastrointestinal disorders
DYSPHAGIA
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
MELAENA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
CONSTIPATION
subjects affected / exposed	2 / 5 (40.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 10 (10.00%)	7 / 40 (17.50%)	8 / 39 (20.51%)	1 / 4 (25.00%)
occurrences all number	2	0	1	1	1	1	10	8	1
VOMITING
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	5 / 40 (12.50%)	4 / 39 (10.26%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0	5	4	0
FLATULENCE
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
ASCITES
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
GASTRITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
DRY MOUTH
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0	1	1	0
RECTAL HAEMORRHAGE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
UMBILICAL HERNIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
ABDOMINAL PAIN UPPER
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0	5	3	0
TOOTHACHE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	2	0
HAEMORRHOIDAL HAEMORRHAGE
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
DIARRHOEA
subjects affected / exposed	1 / 5 (20.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 10 (20.00%)	17 / 40 (42.50%)	13 / 39 (33.33%)	2 / 4 (50.00%)
occurrences all number	1	3	1	1	3	4	24	23	2
DENTAL CARIES
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	1	0	1
NAUSEA
subjects affected / exposed	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 10 (0.00%)	8 / 40 (20.00%)	5 / 39 (12.82%)	1 / 4 (25.00%)
occurrences all number	0	2	0	1	2	0	10	5	2
ABDOMINAL PAIN
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	6 / 40 (15.00%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	1	1	6	3	0
ODYNOPHAGIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0
ABDOMINAL DISTENSION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	1	0
DYSPEPSIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	1	1	0
Hepatobiliary disorders
OCULAR ICTERUS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
DYSHIDROTIC ECZEMA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
HYPERHIDROSIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	3	0
RASH
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	4 / 10 (40.00%)	5 / 40 (12.50%)	7 / 39 (17.95%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	3	5	5	10	1
SKIN ULCER
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
RASH ERYTHEMATOUS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	2	0
PRURITUS
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	2 / 39 (5.13%)	1 / 4 (25.00%)
occurrences all number	1	1	0	0	0	0	4	3	1
RASH MACULO-PAPULAR
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	3 / 39 (7.69%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	4	0
SKIN EXFOLIATION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
DRY SKIN
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 40 (2.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	2	0
NIGHT SWEATS
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0	4	0	0
PETECHIAE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
URTICARIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	2	1	0
HAEMATURIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0
DYSURIA
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0	4	2	0
RENAL FAILURE
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0
Endocrine disorders
DIABETES INSIPIDUS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
HYPOTHYROIDISM
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	5 / 40 (12.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0	7	1	0
TENDONITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
NECK PAIN
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	2	1	0
BACK PAIN
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	5 / 40 (12.50%)	6 / 39 (15.38%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	5	7	0
DIASTASIS RECTI ABDOMINIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	3	0
ARTHRITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0
SACRAL PAIN
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
ARTHRALGIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	7 / 40 (17.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	1	3	0	1	0	9	2	0
MYALGIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	1	4	0	0
PAIN IN EXTREMITY
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 10 (30.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	3	2	2	0
Infections and infestations
SINUSITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	5	0	0
BRONCHITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	4	0	0
HERPES ZOSTER
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	2	0
TONSILLITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
INFLUENZA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	1	1	0	0
NASOPHARYNGITIS
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	8 / 40 (20.00%)	2 / 39 (5.13%)	1 / 4 (25.00%)
occurrences all number	1	1	0	0	1	2	11	2	1
CONJUNCTIVITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	1	1	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	6 / 40 (15.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	2	1	4	0	1	1	9	2	0
PNEUMONIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 40 (10.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	6	0	0
GASTROENTERITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
ORAL CANDIDIASIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 40 (5.00%)	1 / 39 (2.56%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	2	1	0
RHINITIS
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 40 (7.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	3	0	0
ORAL HERPES
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	7 / 40 (17.50%)	3 / 39 (7.69%)	1 / 4 (25.00%)
occurrences all number	0	1	1	0	0	0	13	3	1
CYTOMEGALOVIRUS INFECTION
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
CANDIDA INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	4 / 39 (10.26%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	1	5	4	0
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
HYPERGLYCAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	4 / 39 (10.26%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	2	4	0
GOUT
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
HYPOKALAEMIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	2 / 40 (5.00%)	4 / 39 (10.26%)	1 / 4 (25.00%)
occurrences all number	0	3	3	0	1	2	6	5	2
DECREASED APPETITE
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	8 / 40 (20.00%)	6 / 39 (15.38%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	0	0	8	6	1
HYPOPHOSPHATAEMIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0	2	0	0
HYPOCALCAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	4 / 39 (10.26%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	1	7	0
HYPONATRAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 40 (2.50%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	1	2	0
HYPERPHOSPHATAEMIA
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0	2	0	0
VITAMIN D DEFICIENCY
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
DEHYDRATION
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
HYPOMAGNESAEMIA
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	5 / 40 (12.50%)	5 / 39 (12.82%)	0 / 4 (0.00%)
occurrences all number	5	1	0	1	0	1	13	9	0
HYPOPROTEINAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 40 (5.00%)	2 / 39 (5.13%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	0	2	2	1
HYPOALBUMINAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 40 (2.50%)	0 / 39 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0
DYSLIPIDAEMIA
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	0 / 39 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
HYPERURICAEMIA
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 40 (0.00%)	2 / 39 (5.13%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	2	0

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Were there any global substantial amendments to the protocol? Yes

26 Jul 2017

The study design was updated to include a dose-escalation phase in R/R DLBCL participants. The collection of human anti-chimeric antibodies in relation to rituximab was added as an immunogenicity objective. Eligibility criteria were added to exclude participants with suspected active or latent tuberculosis. Enrollment rules into the dose-escalation phase have been updated for participants’ safety considerations. Few clarifications have been added.

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with Dose-Limiting Toxicities (DLTs)

Primary: Percentage of Participants with Dose-Limiting Toxicities (DLTs)

Primary: Percentage of Participants with Adverse Events (AEs)

Primary: Percentage of Participants with Adverse Events (AEs)

Primary: Percentage of Participants with Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans

Primary: Percentage of Participants with Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans

Secondary: Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with CR at EOI, Determined by Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with CR at EOI, Determined by Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans

Secondary: Percentage of Participants with Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans

Secondary: Percentage of Participants with Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans

Secondary: Percentage of Participants with Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans

Secondary: Percentage of Participants with Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Observed Serum Obinutuzumab Concentration

Secondary: Observed Serum Obinutuzumab Concentration

Secondary: Observed Serum Rituximab Concentration

Secondary: Observed Serum Rituximab Concentration

Secondary: Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody

Secondary: Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody

Secondary: Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)

Secondary: Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)

Secondary: Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

Secondary: Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

Secondary: Observed Plasma Lenalidomide Concentration

Secondary: Observed Plasma Lenalidomide Concentration

Secondary: Number of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab

Secondary: Number of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab

Secondary: Number of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab

Secondary: Number of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab

Secondary: Number of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

Secondary: Number of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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