Download PDF

Clinical Trial Results:
A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination with Brentuximab Vedotin in Subjects with Relapsed Refractory Non Hodgkin Lymphomas with CD30 Expression CheckMate 436: CHECKpoint pathway and nivolumab clinical Trial Evaluation

Summary
EudraCT number	2015-003286-28
Trial protocol	ES FR GB IT
Global end of trial date	07 Feb 2022

Results information
Results version number	v1(current)
This version publication date	23 Feb 2023
First version publication date	23 Feb 2023
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CA209-436

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chausse de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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

30 Mar 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to evaluate the safety profile, tolerability and antitumor activity following administration of nivolumab in combination with brentuximab vedotin in subjects with the diagnosis of relapsed/refractory DLBCL, PTCL (all subtypes excluding ALCL), PMBL. MGZL and CTCL (MF/SS).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Dec 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 23

Country: Number of subjects enrolled

France: 15

Country: Number of subjects enrolled

Italy: 46

Country: Number of subjects enrolled

Spain: 7

Country: Number of subjects enrolled

United Kingdom: 47

Country: Number of subjects enrolled

United States: 6

Worldwide total number of subjects

144

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)

108

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

The Dose Evaluation Phase (Cohort A) will include a dose limiting toxicity (DLT) evaluation for the dose level of brentuximab vedotin 1.8 mg/kg in combination with nivolumab 240 mg. The reduced dose of brentuximab vedotin at 1.2 mg/kg was not needed based on the safety data reviewed throughout the DLT evaluation period.

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

Diffuse Large B-cell Lymphoma (DLBCL)

Arm description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Arm type

Experimental

Investigational medicinal product name

brentuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

1.8mg/kg q3

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

240mg

Peripheral T-cell Lymphoma (PTCL)

Arm description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Arm type

Experimental

Investigational medicinal product name

brentuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

1.8mg/kg q3

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

240mg

Cutaneous T-cell lymphoma (CTCL)

Arm description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Arm type

Experimental

Investigational medicinal product name

brentuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

1.8mg/kg q3

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

240mg

Mediastinal Grey Zone Lymphoma (MGZL)

Arm description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Arm type

Experimental

Investigational medicinal product name

brentuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

1.8mg/kg q3

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

240mg

Primary Mediastinal B-cell Lymphoma (PMBL)

Arm description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Arm type

Experimental

Investigational medicinal product name

brentuximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

1.8mg/kg q3

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravascular use

Dosage and administration details

240mg

Number of subjects in period 1	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Started	42	33	29	10	30
Phase 1 DLT evaluable participants	2	1	3	0	0
Completed Phase 1 DLT evaluation	2	1	3	0	0
Completed	0	0	0	0	0
Not completed	42	33	29	10	30
Poor/Non-Compliance	-	-	1	-	-
Disease progression	29	19	13	5	8
Study drug toxicity	4	6	7	-	3
Request to discontinue	1	-	3	-	1
Other Reasons	1	-	2	2	3
Maximum clinical benefit	1	7	1	3	13
AE unrelated to study drug	3	1	1	-	2
participant withdrew consent	3	-	1	-	-

Baseline characteristics

Top of page

Reporting group title

Diffuse Large B-cell Lymphoma (DLBCL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Peripheral T-cell Lymphoma (PTCL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Cutaneous T-cell lymphoma (CTCL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Mediastinal Grey Zone Lymphoma (MGZL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Primary Mediastinal B-cell Lymphoma (PMBL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)	Total
Number of subjects	42	33	29	10	30	144
Age categorical
Units: Subjects
Adults (18-64 years)	29	21	20	9	29	108
From 65-84 years	12	12	9	1	1	35
85 years and over	1	0	0	0	0	1
Age Continuous
Units: Years
arithmetic mean (standard deviation)	57.7 ( 13.2 )	59.1 ( 12.0 )	57.9 ( 12.39 )	39.9 ( 15.2 )	37.3 ( 12.9 )	-
Sex: Female, Male
Units: Participants
Female	20	11	13	4	17	65
Male	22	22	16	6	13	79
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0
Asian	3	0	0	0	1	4
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	3	2	5	1	2	13
White	36	30	24	9	26	125
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	1	0	0	1	2
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	2	0	0	1	4
Not Hispanic or Latino	14	13	16	6	9	58
Unknown or Not Reported	27	18	13	4	20	82

End points

Top of page

Reporting group title

Diffuse Large B-cell Lymphoma (DLBCL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Peripheral T-cell Lymphoma (PTCL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Cutaneous T-cell lymphoma (CTCL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Mediastinal Grey Zone Lymphoma (MGZL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

Primary Mediastinal B-cell Lymphoma (PMBL)

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Primary: Safety Analysis - Number of participant deaths

Top of page

End point title

Safety Analysis - Number of participant deaths ^[1]

End point description

Number of participant Deaths

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	24	22	3	3	5

No statistical analyses for this end point

Primary: Safety Analysis - Number of participants with adverse advents

Top of page

End point title

Safety Analysis - Number of participants with adverse advents ^[2]

End point description

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[2] - 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 Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	42	33	29	10	30

No statistical analyses for this end point

Primary: Safety Analysis - Number of participants with serious adverse events

Top of page

End point title

Safety Analysis - Number of participants with serious adverse events ^[3]

End point description

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: - results in death - is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) - requires inpatient hospitalization or causes prolongation of existing hospitalization. - results in persistent or significant disability/incapacity - is a congenital anomaly/birth defect - is an important medical event

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 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 Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	22	19	14	4	10

No statistical analyses for this end point

Primary: Safety Analysis - Number of participants with adverse events leading to discontinuation

Top of page

End point title

Safety Analysis - Number of participants with adverse events leading to discontinuation ^[4]

End point description

Number of participants with adverse events leading to discontinuation

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

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: No Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	11	10	6	2	8

No statistical analyses for this end point

Primary: Safety Analysis - Number of participants with adverse events leading to dose delay or reduction

Top of page

End point title

Safety Analysis - Number of participants with adverse events leading to dose delay or reduction ^[5]

End point description

Number of participants with adverse events leading to dose delay or reduction

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	16	15	14	3	17

No statistical analyses for this end point

Primary: Safety Analysis - Number of participants with drug related adverse events

Top of page

End point title

Safety Analysis - Number of participants with drug related adverse events ^[6]

End point description

Number of participants with Drug Related Adverse Events

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[6] - 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 Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	35	27	25	9	25

No statistical analyses for this end point

Primary: Safety Analysis - Percentage of participants with Thyroid test abnormalities

Top of page

End point title

Safety Analysis - Percentage of participants with Thyroid test abnormalities ^[7]

End point description

Percentage of participants with specific thyroid test abnormalities

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	26	27	22	9	25
Units: Percentage of Participants
number (not applicable)
TSH > ULN	34.6	29.6	18.2	11.1	24.0
TSH > ULN w/ TSH ≤ ULN at baseline	26.9	22.2	18.2	0	8.0
TSH > ULN w/at least 1 FT3/FT4 value < LLN	11.5	11.1	13.6	0	4.0
TSH > ULN w/all other FT3/FT4 values ≥ LLN	15.4	11.1	0	11.1	8.0
TSH > ULN with FT3/FT4 testing missing	7.7	7.4	4.5	0	12.0
TSH < LLN	7.7	7.4	4.5	11.1	24.0
TSH < LLN w/TSH ≥ LLN at baseline	7.7	0	4.5	0	20.0
TSH < LLN w/at least 1 FT3/FT4 value > ULN	0	3.7	4.5	0	20.0
TSH < LLN w/ all other FT3/FT4 values ≤ ULN	0	3.7	0	11.1	0
TSH < LLN w/ FT3/FT4 test missing	7.7	0	0	0	4.0

No statistical analyses for this end point

Primary: Safety Analysis - Percentage of participants with Liver test abnormalities

Top of page

End point title

Safety Analysis - Percentage of participants with Liver test abnormalities ^[8]

End point description

Percentage of participants with specific Liver test abnormalities

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[8] - 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 Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Percentage of Participants
number (not applicable)
ALT or AST > 3 x ULN	4.8	6.1	13.8	20.0	24.0
ALT or AST > 5 x ULN	2.4	0	6.9	10.0	10.0
ALT or AST > 10 x ULN	0	0	0	10.0	6.7
ALT or AST > 20 x ULN	0	0	0	10.0	6.7
Total Bilirubin > 2 x ULN	0	6.1	3.4	20.0	3.3
ALT/AST elevation > 3xULN w/Bili >2xULN in 1 day	0	3.0	3.4	10.0	3.3
ALT/AST elevation >3xULN w/Bili 2xULN in 30 days	0	3.0	3.4	10.0	3.3

No statistical analyses for this end point

Primary: Objective Response Rate (ORR)

Top of page

End point title

Objective Response Rate (ORR) ^[9]

End point description

The percentage of participants with a best overall response (BOR) of CR or PR. DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment.

End point type

Primary

End point timeframe

CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Percentage of participants
number (confidence interval 80%)	28.6 (19.4 to 39.4)	45.5 (33.3 to 58.0)	41.4 (28.8 to 55.0)	70.0 (44.8 to 88.4)	73.3 (60.3 to 83.8)

No statistical analyses for this end point

Primary: Safety Analysis - Number of participants with dose limiting toxicities (DLT) in the DLT evaluation phase

Top of page

End point title

Safety Analysis - Number of participants with dose limiting toxicities (DLT) in the DLT evaluation phase ^[10]

End point description

DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.

End point type

Primary

End point timeframe

From first dose of treatment to 6 weeks after first dose

Notes
[10] - 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 Statistical Analysis done for this endpoint

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	2	1	3	0 ^[11]	0 ^[12]
Units: Participants	0	0	0

Notes
[11] - No subjects with reportable measures
[12] - No subjects with reportable measures

No statistical analyses for this end point

Secondary: Duration of Response (DOR)

Top of page

End point title

Duration of Response (DOR)

End point description

DOR will be calculated from the date of initial documentation of a response (CR, or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever occurs first. DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment. Here "99999" means NA

End point type

Secondary

End point timeframe

From the first patient first visit to 8 months after the last patient first visit (up to 48 months)

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	12	15	12	7	22
Units: Months
median (confidence interval 95%)	3.55 (1.18 to 36.53)	4.60 (2.76 to 12.75)	26.97 (2.79 to 99999)	20.76 (1.22 to 99999)	99999 (23.33 to 99999)

No statistical analyses for this end point

Secondary: Complete Response Rate (CRR)

Top of page

End point title

Complete Response Rate (CRR)

End point description

The CRR is defined as the percentage of participants with a BOR (Best overall response) of CR divided by the number of treated participants. DLBCL, PTCL, PMBL & MGZL (CR) 1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR) 1. 100% clearance of skin lesions. 2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma. 3. organs should not be enlarged on examination or imaging 4.absence of blood involvement

End point type

Secondary

End point timeframe

From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Percentage of Participants
number (not applicable)	7.1	33.3	3.4	50.0	40.0

No statistical analyses for this end point

Secondary: Duration of Complete Response

Top of page

End point title

Duration of Complete Response

End point description

The duration of CR will only be evaluated in participants with BOR of CR and is defined as the time from first documentation of CR to the date of relapse or death due to any cause, whichever occurs first. DLBCL, PTCL, PMBL & MGZL (CR) 1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR) 1. 100% clearance of skin lesions. 2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma. 3. organs should not be enlarged on examination or imaging 4.absence of blood involvement Here "99999" means NA

End point type

Secondary

End point timeframe

From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	3	11	1	5	12
Units: Months
median (confidence interval 95%)	36.53 (9.92 to 99999)	7.39 (2.17 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (27.89 to 99999)

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS)

Top of page

End point title

Progression Free Survival (PFS)

End point description

PFS is defined as the time from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment. Participants who did not have any onstudy tumor assessments and did not die will be censored on the date of first treatment. For participants who received subsequent therapy prior to documented progression, it will be censored on the last tumor assessment date prior to or on subsequent therapy. Here "99999" means NA

End point type

Secondary

End point timeframe

From first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. (about 48 months)

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Months
median (confidence interval 95%)	2.60 (1.38 to 2.79)	4.30 (1.58 to 5.62)	15.61 (4.86 to 99999)	21.88 (0.07 to 99999)	25.95 (2.63 to 99999)

No statistical analyses for this end point

Secondary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

OS is defined as the time from the date of first dose of study drug until the date of death (any reason). If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive. Here "99999" means NA

End point type

Secondary

End point timeframe

From the first patient first visit to 8 months after the last patient first visit (about 48 months)

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Months
median (confidence interval 95%)	13.31 (6.57 to 15.87)	11.07 (5.16 to 15.31)	37.16 (18.63 to 99999)	99999 (0.07 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Post-hoc: Safety Analysis - Number of participant deaths - Extended collection

Top of page

End point title

Safety Analysis - Number of participant deaths - Extended collection

End point description

Number of participant Deaths This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)

End point type

Post-hoc

End point timeframe

from first date of treatment to final database lock. Approximately 6 years and 7 months.

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	30	26	14	4	8

No statistical analyses for this end point

Post-hoc: Safety Analysis - Number of participants with Adverse Events - Extended Collection

Top of page

End point title

Safety Analysis - Number of participants with Adverse Events - Extended Collection

End point description

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)

End point type

Post-hoc

End point timeframe

From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	42	33	29	10	30

No statistical analyses for this end point

Post-hoc: Safety Analysis - Number of participants with Serious Adverse Events - Extended Collection

Top of page

End point title

Safety Analysis - Number of participants with Serious Adverse Events - Extended Collection

End point description

End point type

Post-hoc

End point timeframe

From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	22	19	14	4	10

No statistical analyses for this end point

Post-hoc: Safety Analysis - Number of participants with Adverse Events leading to discontinuation - Extended Collection

Top of page

End point title

Safety Analysis - Number of participants with Adverse Events leading to discontinuation - Extended Collection

End point description

Number of Adverse events leading to discontinuation This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)

End point type

Post-hoc

End point timeframe

From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	12	11	10	2	9

No statistical analyses for this end point

Post-hoc: Safety Analysis - Number of participants with Drug Related Adverse Events - Extended Collection

Top of page

End point title

Safety Analysis - Number of participants with Drug Related Adverse Events - Extended Collection

End point description

Number of Drug Related Adverse Events This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)

End point type

Post-hoc

End point timeframe

From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.

End point values	Diffuse Large B-cell Lymphoma (DLBCL)	Peripheral T-cell Lymphoma (PTCL)	Cutaneous T-cell lymphoma (CTCL)	Mediastinal Grey Zone Lymphoma (MGZL)	Primary Mediastinal B-cell Lymphoma (PMBL)
Number of subjects analysed	42	33	29	10	30
Units: Participants	35	28	26	9	25

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first patient first visit to first to final data base lock. Approximately 6 years and 7 months. All cause mortality is calculated from first treatment to final data base lock.. Approximately 6 years and 7 months.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

DLBCL

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

PMBL

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

MGZL

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

PTCL

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Reporting group title

CTCL

Reporting group description

1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

Serious adverse events	DLBCL	PMBL	MGZL	PTCL	CTCL
Total subjects affected by serious adverse events
subjects affected / exposed	23 / 42 (54.76%)	12 / 30 (40.00%)	5 / 10 (50.00%)	25 / 33 (75.76%)	18 / 29 (62.07%)
number of deaths (all causes)	30	8	4	26	14
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Lymphoma
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Malignant neoplasm progression
subjects affected / exposed	13 / 42 (30.95%)	2 / 30 (6.67%)	1 / 10 (10.00%)	9 / 33 (27.27%)	4 / 29 (13.79%)
occurrences causally related to treatment / all	0 / 14	0 / 2	0 / 1	0 / 9	0 / 4
deaths causally related to treatment / all	0 / 10	0 / 2	0 / 1	0 / 9	0 / 4
Neoplasm malignant
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Vascular disorders
Haematoma
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Haemorrhage
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Embolism
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Deep vein thrombosis
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
General physical health deterioration
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Influenza like illness
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Pain
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Pyrexia
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	1 / 10 (10.00%)	10 / 33 (30.30%)	2 / 29 (6.90%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 1	3 / 11	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Reproductive system and breast disorders
Oedema genital
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Acute respiratory failure
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Pleural effusion
subjects affected / exposed	2 / 42 (4.76%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Delirium
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Investigations
Lipase increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium test positive
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Transaminases increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Overdose
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Congenital, familial and genetic disorders
Aplasia
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Atrioventricular block complete
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Pericardial effusion
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Nervous system disorders
Dysmetria
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Syncope
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Paraparesis
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	3 / 42 (7.14%)	2 / 30 (6.67%)	1 / 10 (10.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 2	2 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Pancreatitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Immune-mediated hepatitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Jaundice cholestatic
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erythema multiforme
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dermatitis exfoliative generalised
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Nephroangiosclerosis
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Clostridium difficile colitis
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Clostridium difficile infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Device related infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Lung abscess
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Pneumonia
subjects affected / exposed	4 / 42 (9.52%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	2 / 5	0 / 1	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Respiratory tract infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Sepsis
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Vascular device infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Skin infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	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
Staphylococcal infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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
Hypokalaemia
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences causally related to treatment / all	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

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

Non-serious adverse events	DLBCL	PMBL	MGZL	PTCL	CTCL
Total subjects affected by non serious adverse events
subjects affected / exposed	42 / 42 (100.00%)	28 / 30 (93.33%)	9 / 10 (90.00%)	33 / 33 (100.00%)	28 / 29 (96.55%)
Vascular disorders
Hot flush
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	4	0	0	0	0
Hypotension
subjects affected / exposed	9 / 42 (21.43%)	0 / 30 (0.00%)	0 / 10 (0.00%)	4 / 33 (12.12%)	2 / 29 (6.90%)
occurrences all number	10	0	0	4	2
Hypertension
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	2 / 10 (20.00%)	3 / 33 (9.09%)	3 / 29 (10.34%)
occurrences all number	0	0	2	3	3
General disorders and administration site conditions
Asthenia
subjects affected / exposed	11 / 42 (26.19%)	4 / 30 (13.33%)	0 / 10 (0.00%)	7 / 33 (21.21%)	5 / 29 (17.24%)
occurrences all number	12	4	0	7	7
Fatigue
subjects affected / exposed	16 / 42 (38.10%)	2 / 30 (6.67%)	1 / 10 (10.00%)	15 / 33 (45.45%)	8 / 29 (27.59%)
occurrences all number	16	2	1	18	8
Chills
subjects affected / exposed	7 / 42 (16.67%)	2 / 30 (6.67%)	0 / 10 (0.00%)	2 / 33 (6.06%)	2 / 29 (6.90%)
occurrences all number	11	2	0	3	2
Chest pain
subjects affected / exposed	1 / 42 (2.38%)	2 / 30 (6.67%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	1	3	1	0	0
Gait disturbance
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences all number	1	0	1	0	1
Malaise
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	0	2	0
Oedema peripheral
subjects affected / exposed	4 / 42 (9.52%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	7 / 29 (24.14%)
occurrences all number	4	1	0	2	7
Pain
subjects affected / exposed	1 / 42 (2.38%)	4 / 30 (13.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences all number	1	4	0	1	0
Peripheral swelling
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	3	0	0	0	0
Pyrexia
subjects affected / exposed	13 / 42 (30.95%)	7 / 30 (23.33%)	2 / 10 (20.00%)	12 / 33 (36.36%)	14 / 29 (48.28%)
occurrences all number	17	10	3	20	17
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	5 / 42 (11.90%)	3 / 30 (10.00%)	1 / 10 (10.00%)	7 / 33 (21.21%)	4 / 29 (13.79%)
occurrences all number	5	4	1	7	4
Dysphonia
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	4	0	0	1	2
Cough
subjects affected / exposed	10 / 42 (23.81%)	13 / 30 (43.33%)	3 / 10 (30.00%)	9 / 33 (27.27%)	6 / 29 (20.69%)
occurrences all number	10	15	4	9	9
Pneumonitis
subjects affected / exposed	2 / 42 (4.76%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	2	1	0	2	0
Oropharyngeal pain
subjects affected / exposed	4 / 42 (9.52%)	2 / 30 (6.67%)	0 / 10 (0.00%)	3 / 33 (9.09%)	0 / 29 (0.00%)
occurrences all number	4	4	0	3	0
Nasal congestion
subjects affected / exposed	2 / 42 (4.76%)	1 / 30 (3.33%)	1 / 10 (10.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	2	1	2	3	2
Hypoxia
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	1	0	2	0
Dyspnoea exertional
subjects affected / exposed	6 / 42 (14.29%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	7	1	0	2	0
Productive cough
subjects affected / exposed	4 / 42 (9.52%)	2 / 30 (6.67%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences all number	9	3	0	2	0
Psychiatric disorders
Anxiety
subjects affected / exposed	3 / 42 (7.14%)	2 / 30 (6.67%)	0 / 10 (0.00%)	2 / 33 (6.06%)	2 / 29 (6.90%)
occurrences all number	3	2	0	2	2
Insomnia
subjects affected / exposed	5 / 42 (11.90%)	2 / 30 (6.67%)	2 / 10 (20.00%)	1 / 33 (3.03%)	4 / 29 (13.79%)
occurrences all number	6	2	2	1	4
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	2 / 10 (20.00%)	6 / 33 (18.18%)	2 / 29 (6.90%)
occurrences all number	0	1	3	7	3
Amylase increased
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	0 / 10 (0.00%)	3 / 33 (9.09%)	3 / 29 (10.34%)
occurrences all number	1	1	0	4	3
Aspartate aminotransferase increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	2 / 10 (20.00%)	6 / 33 (18.18%)	3 / 29 (10.34%)
occurrences all number	0	0	2	8	4
Blood alkaline phosphatase increased
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	2	0	1	3	0
Blood bilirubin increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	2	2	0
Blood creatinine increased
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	1 / 10 (10.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	3	0	1	1	1
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)	0 / 29 (0.00%)
occurrences all number	2	0	0	3	0
Lipase increased
subjects affected / exposed	2 / 42 (4.76%)	1 / 30 (3.33%)	0 / 10 (0.00%)	3 / 33 (9.09%)	4 / 29 (13.79%)
occurrences all number	2	1	0	3	6
Lymphocyte count decreased
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)	2 / 29 (6.90%)
occurrences all number	0	0	0	3	3
Neutrophil count decreased
subjects affected / exposed	2 / 42 (4.76%)	2 / 30 (6.67%)	0 / 10 (0.00%)	5 / 33 (15.15%)	0 / 29 (0.00%)
occurrences all number	6	4	0	8	0
Platelet count decreased
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	0 / 10 (0.00%)	3 / 33 (9.09%)	2 / 29 (6.90%)
occurrences all number	1	1	0	3	2
Weight decreased
subjects affected / exposed	4 / 42 (9.52%)	2 / 30 (6.67%)	1 / 10 (10.00%)	2 / 33 (6.06%)	3 / 29 (10.34%)
occurrences all number	4	2	1	2	3
Weight increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences all number	0	0	1	0	1
White blood cell count decreased
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences all number	1	0	0	3	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences all number	3	0	0	0	1
Infusion related reaction
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	1 / 10 (10.00%)	4 / 33 (12.12%)	6 / 29 (20.69%)
occurrences all number	0	1	2	4	18
Procedural nausea
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	2	0	0	0
Cardiac disorders
Sinus bradycardia
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	1	0	0
Sinus tachycardia
subjects affected / exposed	2 / 42 (4.76%)	2 / 30 (6.67%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences all number	2	2	0	1	0
Tachycardia
subjects affected / exposed	2 / 42 (4.76%)	2 / 30 (6.67%)	1 / 10 (10.00%)	0 / 33 (0.00%)	2 / 29 (6.90%)
occurrences all number	2	2	1	0	2
Nervous system disorders
Neuropathy peripheral
subjects affected / exposed	14 / 42 (33.33%)	9 / 30 (30.00%)	0 / 10 (0.00%)	5 / 33 (15.15%)	9 / 29 (31.03%)
occurrences all number	15	11	0	5	12
Paraesthesia
subjects affected / exposed	3 / 42 (7.14%)	2 / 30 (6.67%)	3 / 10 (30.00%)	5 / 33 (15.15%)	1 / 29 (3.45%)
occurrences all number	3	2	3	5	1
Headache
subjects affected / exposed	6 / 42 (14.29%)	6 / 30 (20.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)	4 / 29 (13.79%)
occurrences all number	9	6	0	7	4
Dysgeusia
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	3 / 33 (9.09%)	1 / 29 (3.45%)
occurrences all number	0	1	0	3	1
Peripheral sensory neuropathy
subjects affected / exposed	1 / 42 (2.38%)	5 / 30 (16.67%)	2 / 10 (20.00%)	5 / 33 (15.15%)	3 / 29 (10.34%)
occurrences all number	1	5	2	5	3
Dizziness
subjects affected / exposed	3 / 42 (7.14%)	1 / 30 (3.33%)	0 / 10 (0.00%)	3 / 33 (9.09%)	1 / 29 (3.45%)
occurrences all number	3	1	0	4	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	5 / 42 (11.90%)	3 / 30 (10.00%)	6 / 10 (60.00%)	10 / 33 (30.30%)	1 / 29 (3.45%)
occurrences all number	8	3	6	25	1
Eosinophilia
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	2	0	0	0
Thrombocytopenia
subjects affected / exposed	5 / 42 (11.90%)	5 / 30 (16.67%)	3 / 10 (30.00%)	8 / 33 (24.24%)	1 / 29 (3.45%)
occurrences all number	8	8	4	10	1
Neutropenia
subjects affected / exposed	8 / 42 (19.05%)	13 / 30 (43.33%)	4 / 10 (40.00%)	9 / 33 (27.27%)	0 / 29 (0.00%)
occurrences all number	20	23	5	23	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences all number	1	0	0	2	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	10 / 42 (23.81%)	4 / 30 (13.33%)	0 / 10 (0.00%)	9 / 33 (27.27%)	1 / 29 (3.45%)
occurrences all number	15	5	0	12	1
Abdominal pain lower
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	0	0	0	4	2
Abdominal pain upper
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	1 / 10 (10.00%)	2 / 33 (6.06%)	2 / 29 (6.90%)
occurrences all number	0	2	1	4	3
Diarrhoea
subjects affected / exposed	20 / 42 (47.62%)	4 / 30 (13.33%)	0 / 10 (0.00%)	14 / 33 (42.42%)	15 / 29 (51.72%)
occurrences all number	41	6	0	27	21
Constipation
subjects affected / exposed	9 / 42 (21.43%)	5 / 30 (16.67%)	1 / 10 (10.00%)	8 / 33 (24.24%)	3 / 29 (10.34%)
occurrences all number	13	5	1	11	3
Dyspepsia
subjects affected / exposed	2 / 42 (4.76%)	3 / 30 (10.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	4 / 29 (13.79%)
occurrences all number	3	4	0	2	4
Dysphagia
subjects affected / exposed	3 / 42 (7.14%)	1 / 30 (3.33%)	0 / 10 (0.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences all number	4	1	0	2	1
Flatulence
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	0	2	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	0	2	0	1	2
Haemorrhoids
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	0	3	0
Stomatitis
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	0 / 10 (0.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences all number	0	2	0	3	1
Nausea
subjects affected / exposed	17 / 42 (40.48%)	5 / 30 (16.67%)	0 / 10 (0.00%)	12 / 33 (36.36%)	10 / 29 (34.48%)
occurrences all number	20	9	0	18	11
Toothache
subjects affected / exposed	0 / 42 (0.00%)	2 / 30 (6.67%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	2	1	0	0
Vomiting
subjects affected / exposed	9 / 42 (21.43%)	3 / 30 (10.00%)	0 / 10 (0.00%)	8 / 33 (24.24%)	3 / 29 (10.34%)
occurrences all number	10	5	0	12	3
Skin and subcutaneous tissue disorders
Hyperhidrosis
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	1	0	0	2
Dry skin
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	4 / 33 (12.12%)	2 / 29 (6.90%)
occurrences all number	1	0	0	4	2
Dermatitis exfoliative generalised
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	4 / 29 (13.79%)
occurrences all number	0	0	0	0	4
Alopecia
subjects affected / exposed	4 / 42 (9.52%)	1 / 30 (3.33%)	0 / 10 (0.00%)	3 / 33 (9.09%)	3 / 29 (10.34%)
occurrences all number	5	1	0	4	3
Night sweats
subjects affected / exposed	6 / 42 (14.29%)	2 / 30 (6.67%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	10	2	0	2	0
Rash maculo-papular
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	3 / 29 (10.34%)
occurrences all number	2	0	3	2	3
Rash macular
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	0	0	0	2
Rash
subjects affected / exposed	5 / 42 (11.90%)	6 / 30 (20.00%)	0 / 10 (0.00%)	9 / 33 (27.27%)	4 / 29 (13.79%)
occurrences all number	7	8	0	13	8
Pruritus
subjects affected / exposed	3 / 42 (7.14%)	4 / 30 (13.33%)	1 / 10 (10.00%)	10 / 33 (30.30%)	8 / 29 (27.59%)
occurrences all number	4	5	1	13	10
Petechiae
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	0	2	0
Skin exfoliation
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	3 / 29 (10.34%)
occurrences all number	0	0	0	0	3
Skin lesion
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	0	1	0	1	2
Skin ulcer
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	1	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	3 / 29 (10.34%)
occurrences all number	1	0	0	1	3
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 42 (0.00%)	4 / 30 (13.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences all number	0	4	0	1	0
Hypothyroidism
subjects affected / exposed	1 / 42 (2.38%)	2 / 30 (6.67%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	1	2	0	1	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	8 / 42 (19.05%)	6 / 30 (20.00%)	1 / 10 (10.00%)	7 / 33 (21.21%)	4 / 29 (13.79%)
occurrences all number	11	7	1	9	4
Bone pain
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	1	1	1	2	0
Back pain
subjects affected / exposed	3 / 42 (7.14%)	3 / 30 (10.00%)	1 / 10 (10.00%)	6 / 33 (18.18%)	1 / 29 (3.45%)
occurrences all number	3	3	1	6	1
Pain in extremity
subjects affected / exposed	4 / 42 (9.52%)	3 / 30 (10.00%)	1 / 10 (10.00%)	4 / 33 (12.12%)	0 / 29 (0.00%)
occurrences all number	5	4	1	5	0
Neck pain
subjects affected / exposed	1 / 42 (2.38%)	1 / 30 (3.33%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	1	1	0	2	2
Myalgia
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	3 / 29 (10.34%)
occurrences all number	2	0	0	1	3
Muscular weakness
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)	1 / 29 (3.45%)
occurrences all number	2	0	0	3	1
Muscle spasms
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	1 / 10 (10.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	3	0	1	1	2
Infections and infestations
Ear infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	2 / 29 (6.90%)
occurrences all number	1	0	0	1	2
Nasopharyngitis
subjects affected / exposed	3 / 42 (7.14%)	2 / 30 (6.67%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	3	2	0	0	0
Influenza
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences all number	1	0	0	2	1
Herpes zoster
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	3	0	0	1	1
Oral candidiasis
subjects affected / exposed	2 / 42 (4.76%)	2 / 30 (6.67%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 29 (0.00%)
occurrences all number	2	2	0	2	0
Pneumonia
subjects affected / exposed	5 / 42 (11.90%)	1 / 30 (3.33%)	2 / 10 (20.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	5	1	3	1	1
Rhinitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	1	3	0
Sinusitis
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences all number	4	0	0	0	1
Skin infection
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	1 / 29 (3.45%)
occurrences all number	2	0	1	0	2
Staphylococcal infection
subjects affected / exposed	0 / 42 (0.00%)	1 / 30 (3.33%)	0 / 10 (0.00%)	0 / 33 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	1	0	0	2
Upper respiratory tract infection
subjects affected / exposed	3 / 42 (7.14%)	3 / 30 (10.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	5	3	0	2	1
Urinary tract infection
subjects affected / exposed	4 / 42 (9.52%)	0 / 30 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	1 / 29 (3.45%)
occurrences all number	6	0	2	2	1
Viral infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	0	0	0	2	0
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	0	0	0	2
Decreased appetite
subjects affected / exposed	8 / 42 (19.05%)	3 / 30 (10.00%)	2 / 10 (20.00%)	6 / 33 (18.18%)	5 / 29 (17.24%)
occurrences all number	11	3	2	9	6
Hyperuricaemia
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	2 / 10 (20.00%)	1 / 33 (3.03%)	1 / 29 (3.45%)
occurrences all number	2	0	3	1	1
Hyperkalaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	0	0	0	2
Hyperglycaemia
subjects affected / exposed	2 / 42 (4.76%)	0 / 30 (0.00%)	0 / 10 (0.00%)	4 / 33 (12.12%)	0 / 29 (0.00%)
occurrences all number	5	0	0	4	0
Hypoalbuminaemia
subjects affected / exposed	1 / 42 (2.38%)	0 / 30 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 29 (0.00%)
occurrences all number	1	0	0	2	0
Hypercalcaemia
subjects affected / exposed	3 / 42 (7.14%)	0 / 30 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 29 (0.00%)
occurrences all number	3	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	6 / 42 (14.29%)	1 / 30 (3.33%)	3 / 10 (30.00%)	5 / 33 (15.15%)	1 / 29 (3.45%)
occurrences all number	10	1	4	5	1
Hypokalaemia
subjects affected / exposed	9 / 42 (21.43%)	0 / 30 (0.00%)	3 / 10 (30.00%)	4 / 33 (12.12%)	1 / 29 (3.45%)
occurrences all number	11	0	3	10	1
Hypocalcaemia
subjects affected / exposed	4 / 42 (9.52%)	0 / 30 (0.00%)	1 / 10 (10.00%)	5 / 33 (15.15%)	0 / 29 (0.00%)
occurrences all number	4	0	1	9	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

14 Sep 2016

This amendment will allow additional cohorts in subjects with relapsed PMBL & MGZL to participate in the expansion cohort. Additionally, the amendment will also provide defined Indeterminate response (IR) criteria along with changes in the biomarker section. Minor clarification in the inclusion, exclusion criteria and clarification of dose adjustment for brentuximab vedotin for grade 3 neurological toxicity has also been updated

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination with Brentuximab Vedotin in Subjects with Relapsed Refractory Non Hodgkin Lymphomas with CD30 Expression CheckMate 436: CHECKpoint pathway and nivolumab clinical Trial Evaluation

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety Analysis - Number of participant deaths

Primary: Safety Analysis - Number of participant deaths

Primary: Safety Analysis - Number of participants with adverse advents

Primary: Safety Analysis - Number of participants with adverse advents

Primary: Safety Analysis - Number of participants with serious adverse events

Primary: Safety Analysis - Number of participants with serious adverse events

Primary: Safety Analysis - Number of participants with adverse events leading to discontinuation

Primary: Safety Analysis - Number of participants with adverse events leading to discontinuation

Primary: Safety Analysis - Number of participants with adverse events leading to dose delay or reduction

Primary: Safety Analysis - Number of participants with adverse events leading to dose delay or reduction

Primary: Safety Analysis - Number of participants with drug related adverse events

Primary: Safety Analysis - Number of participants with drug related adverse events

Primary: Safety Analysis - Percentage of participants with Thyroid test abnormalities

Primary: Safety Analysis - Percentage of participants with Thyroid test abnormalities

Primary: Safety Analysis - Percentage of participants with Liver test abnormalities

Primary: Safety Analysis - Percentage of participants with Liver test abnormalities

Primary: Objective Response Rate (ORR)

Primary: Objective Response Rate (ORR)

Primary: Safety Analysis - Number of participants with dose limiting toxicities (DLT) in the DLT evaluation phase

Primary: Safety Analysis - Number of participants with dose limiting toxicities (DLT) in the DLT evaluation phase

Secondary: Duration of Response (DOR)

Secondary: Duration of Response (DOR)

Secondary: Complete Response Rate (CRR)

Secondary: Complete Response Rate (CRR)

Secondary: Duration of Complete Response

Secondary: Duration of Complete Response

Secondary: Progression Free Survival (PFS)

Secondary: Progression Free Survival (PFS)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Post-hoc: Safety Analysis - Number of participant deaths - Extended collection

Post-hoc: Safety Analysis - Number of participant deaths - Extended collection

Post-hoc: Safety Analysis - Number of participants with Adverse Events - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Adverse Events - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Serious Adverse Events - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Serious Adverse Events - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Adverse Events leading to discontinuation - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Adverse Events leading to discontinuation - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Drug Related Adverse Events - Extended Collection

Post-hoc: Safety Analysis - Number of participants with Drug Related Adverse Events - Extended Collection

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination with Brentuximab Vedotin in Subjects with Relapsed Refractory Non Hodgkin Lymphomas with CD30 Expression CheckMate 436: CHECKpoint pathway and nivolumab clinical Trial Evaluation