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Clinical Trial Results:
A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of MK-7684A (MK-7684 [Vibostolimab] with MK-3475 [Pembrolizumab] Coformulation) in Participants with Relapsed or Refractory Hematological Malignancies

Summary
EudraCT number	2021-001700-15
Trial protocol	DE DK FR ES PL IT HU
Global end of trial date	10 Dec 2024

Results information
Results version number	v1(current)
This version publication date	21 Dec 2025
First version publication date	21 Dec 2025
Other versions

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

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Trial information

Top of page

Sponsor protocol code

7684a-004

ISRCTN number

-

US NCT number

NCT05005442

WHO universal trial number (UTN)

-

Sponsor organisation name

Merck Sharp & Dohme LLC

Sponsor organisation address

126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@MSD.com

Scientific contact

Senior Vice President, Global Clinical Development, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@MSD.com

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

10 Dec 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Dec 2024

Global end of trial reached?

Yes

Global end of trial date

10 Dec 2024

Was the trial ended prematurely?

No

Main objective of the trial

The purpose of the study is to determine the safety and tolerability of pembrolizumab/vibostolimab (MK-7684A) in hematological malignancies. This study will also evaluate the overall response rate (ORR), the duration of response (DOR), and disease control rate (DCR) following administration of pembrolizumab/vibostolimab. In addition, this study will characterize pharmacokinetic (PK) profile of vibostolimab (MK-7684).

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

28 Sep 2021

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 7

Country: Number of subjects enrolled

Canada: 4

Country: Number of subjects enrolled

Chile: 8

Country: Number of subjects enrolled

Denmark: 12

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Hungary: 20

Country: Number of subjects enrolled

Israel: 23

Country: Number of subjects enrolled

Italy: 15

Country: Number of subjects enrolled

Poland: 21

Country: Number of subjects enrolled

Russian Federation: 8

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

Taiwan: 4

Country: Number of subjects enrolled

Türkiye: 17

Country: Number of subjects enrolled

Ukraine: 9

Country: Number of subjects enrolled

United States: 17

Worldwide total number of subjects

192

EEA total number of subjects

95

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

122

From 65 to 84 years

66

85 years and over

4

Subject disposition

Top of page

Recruitment details

-

Screening details

One hundred ninety-two participants were allocated, 1 participant was allocated but did not receive treatment due to worsening of underlying disease. No participants were enrolled into Part 2 of the study (The study was closed with amendment 5 after the last subject completed 35 cycles of the first course of Part 1).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort A Pembrolizumab/vibostolimab coformulation

Arm description

Participants with classic Hodgkin’s lymphoma (cHL) or primary mediastinal B‐cell lymphoma (PMBCL) who are relapsed or refractory to at least 1 line of prior therapy (cHL) of at least 2 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Arm type

Experimental

Investigational medicinal product name

Pembrolizumab/vibostolimab coformulation

Investigational medicinal product code

Other name

MK7684A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion

Cohort B Pembrolizumab/vibostolimab coformulation

Arm description

Participants with cHL or PMBCL who are relapsed or refractory to at least 2 lines of prior therapies (cHL) of at least 3 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Arm type

Experimental

Investigational medicinal product name

Pembrolizumab/vibostolimab coformulation

Investigational medicinal product code

Other name

MK7684A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion

Cohort C Pembrolizumab/vibostolimab coformulation

Arm description

Participants with relapsed or refractory follicular lymphoma (FL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Arm type

Experimental

Investigational medicinal product name

Pembrolizumab/vibostolimab coformulation

Investigational medicinal product code

Other name

MK7684A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion

Cohort D Pembrolizumab/vibostolimab coformulation

Arm description

Participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Arm type

Experimental

Investigational medicinal product name

Pembrolizumab/vibostolimab coformulation

Investigational medicinal product code

Other name

MK7684A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion

Cohort E Pembrolizumab/vibostolimab coformulation

Arm description

Participants with relapsed or refractory multiple myeloma (MM) following at least 3 lines of therapy and have exhausted all approved lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Arm type

Experimental

Investigational medicinal product name

Pembrolizumab/vibostolimab coformulation

Investigational medicinal product code

Other name

MK7684A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion

Cohort F Pembrolizumab/vibostolimab coformulation

Arm description

Participants with relapsed or refractory non-Hodgkin’s lymphoma (NHL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Arm type

Experimental

Investigational medicinal product name

Pembrolizumab/vibostolimab coformulation

Investigational medicinal product code

Other name

MK7684A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion

Number of subjects in period 1	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Started	42	42	20	30	25	33
Treated	42	42	20	30	25	32
Completed	0	0	0	0	0	0
Not completed	42	42	20	30	25	33
Adverse event, serious fatal	14	10	8	22	13	15
Consent withdrawn by subject	2	2	1	3	-	5
Physician decision	-	-	1	-	2	-
Site terminated by sponsor	-	2	-	-	-	1
Sponsor decision	26	26	10	5	9	12
Lost to follow-up	-	2	-	-	1	-

Baseline characteristics

Top of page

Reporting group title

Cohort A Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with classic Hodgkin’s lymphoma (cHL) or primary mediastinal B‐cell lymphoma (PMBCL) who are relapsed or refractory to at least 1 line of prior therapy (cHL) of at least 2 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort B Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with cHL or PMBCL who are relapsed or refractory to at least 2 lines of prior therapies (cHL) of at least 3 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort C Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory follicular lymphoma (FL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort D Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort E Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory multiple myeloma (MM) following at least 3 lines of therapy and have exhausted all approved lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort F Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory non-Hodgkin’s lymphoma (NHL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation	Total
Number of subjects	42	42	20	30	25	33	192
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	35	33	11	17	12	14	122
From 65-84 years	7	9	9	12	12	17	66
85 years and over	0	0	0	1	1	2	4
Age Continuous
Units: Years
arithmetic mean (standard deviation)	41.5 ( 16.5 )	46.7 ( 17.6 )	63.6 ( 12.8 )	60.7 ( 12.7 )	64.4 ( 10.8 )	66.0 ( 14.4 )	-
Sex: Female, Male
Units: Participants
Female	18	16	8	15	15	13	85
Male	24	26	12	15	10	20	107
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	0	0	0	2	2	3	7
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	4	1	0	1	3	1	10
White	38	35	20	27	20	29	169
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	6	0	0	0	0	6
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	6	3	3	5	1	3	21
Not Hispanic or Latino	36	33	15	22	24	29	159
Unknown or Not Reported	0	6	2	3	0	1	12

End points

Top of page

Reporting group title

Cohort A Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with classic Hodgkin’s lymphoma (cHL) or primary mediastinal B‐cell lymphoma (PMBCL) who are relapsed or refractory to at least 1 line of prior therapy (cHL) of at least 2 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort B Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with cHL or PMBCL who are relapsed or refractory to at least 2 lines of prior therapies (cHL) of at least 3 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort C Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory follicular lymphoma (FL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort D Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort E Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory multiple myeloma (MM) following at least 3 lines of therapy and have exhausted all approved lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

Cohort F Pembrolizumab/vibostolimab coformulation

Reporting group description

Participants with relapsed or refractory non-Hodgkin’s lymphoma (NHL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Primary: Percentage of Participants with a Dose-Limiting Toxicity (DLT)

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End point title

Percentage of Participants with a Dose-Limiting Toxicity (DLT) ^[1]

End point description

A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Percentage of participants who experience a DLT per CTCAE 5.0 are reported. The analysis population consists of all participants who received at least one dose of study intervention and that finished the DLT evaluation period without a DLT or experienced a DLT in the DLT evaluation period.

End point type

Primary

End point timeframe

Up to approximately 6 weeks

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: Per protocol, no statistical analysis was planned for this endpoint.

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	42	41	18	20	10	25
Units: Percentage of Participants
number (confidence interval 95%)	4.8 (0.8 to 14.2)	2.4 (0.1 to 10.8)	0.0 (0.0 to 14.6)	5.0 (0.3 to 20.8)	0.0 (0.0 to 23.8)	8.0 (1.4 to 22.8)

No statistical analyses for this end point

Primary: Percentage of Participants Who Experienced an Adverse Event (AE)

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End point title

Percentage of Participants Who Experienced an Adverse Event (AE) ^[2]

End point description

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experience an AE are reported. The analysis population included all allocated participants who received at least 1 dose of study intervention.

End point type

Primary

End point timeframe

Up to approximately 27 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: Per protocol, no statistical analysis was planned for this endpoint.

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	42	42	20	30	25	32
Units: Percentage of Participants
number (not applicable)	92.9	97.6	95.0	80.0	80.0	87.5

No statistical analyses for this end point

Primary: Percentage of Participants Who Discontinued Study Treatment Due to an AE

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End point title

Percentage of Participants Who Discontinued Study Treatment Due to an AE ^[3]

End point description

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants discontinued from the study treatment due to an AE are reported. The analysis population included all allocated participants who received at least 1 dose of study intervention.

End point type

Primary

End point timeframe

Up to approximately 24 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: Per protocol, no statistical analysis was planned for this endpoint.

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	42	42	20	30	25	32
Units: Percentage of Participants
number (not applicable)	19.0	4.8	15.0	13.3	4.0	12.5

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR) as assessed by Lugano 2014 Classification (Cohorts A-D & F)

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End point title

Objective Response Rate (ORR) as assessed by Lugano 2014 Classification (Cohorts A-D & F)

End point description

ORR was assessed based on Lugano 2014 Classification. ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and was evaluated using computed tomography (CT) and positron emission tomography (PET)-CT. CR is complete metabolic (no/minimal fluorodeoxyglucose [FDG] uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). ORR for Cohorts A-D and F is presented. Cohort E is presented separately. The analysis population consisted of all participants who have received at least one dose of study intervention and had ORR measured by Lugano 2014 Classification

End point type

Secondary

End point timeframe

Up to approximately 37 months

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	42	42	20	30	0 ^[4]	32
Units: Percentage of Participants
number (confidence interval 95%)	64.3 (48.0 to 78.4)	35.7 (21.6 to 52.0)	15.0 (3.2 to 37.9)	16.7 (5.6 to 34.7)	( to )	18.8 (7.2 to 36.4)

Notes
[4] - ORR for Cohort E is evaluated using IMWG Criteria and is presented separately.

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR) as assessed by the 2016 International Myeloma Working Group (IMWG) Response Criteria (Cohort E)

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End point title

Objective Response Rate (ORR) as assessed by the 2016 International Myeloma Working Group (IMWG) Response Criteria (Cohort E)

End point description

ORR is the percentage of the participants with either a stringent complete response (sCR), CR, very good partial response (VGPR), or PR according to the IMWG Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum Mprotein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. ORR for Cohorts A-D and F were presented in a previous outcome measure. The analysis population included all participants who have received at least one dose of study intervention and had ORR measured by 2016 IMWG Response Criteria.

End point type

Secondary

End point timeframe

Up to approximately 37 months

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	0 ^[5]	0 ^[6]	0 ^[7]	0 ^[8]	25	0 ^[9]
Units: Percentage of Participants
number (confidence interval 95%)	( to )	( to )	( to )	( to )	0.0 (0.0 to 13.7)	( to )

Notes
[5] - ORR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[6] - ORR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[7] - ORR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[8] - ORR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[9] - ORR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.

No statistical analyses for this end point

Secondary: Duration of Response (DOR) as assessed by Lugano 2014 Classification (Cohorts A-D & F)

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End point title

Duration of Response (DOR) as assessed by Lugano 2014 Classification (Cohorts A-D & F)

End point description

For participants who demonstrate a confirmed CR or PR, DOR is defined as the time from CR or PR to documented disease progression or death. Participants are assessed using CT and PET-CT and response was evaluated based on the Lugano 2014 Classification. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters (SPD) for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). DOR for Cohorts A-D and F is presented. Cohort E is presented separately. The analysis population included all participants who have received at least one dose of study intervention and had a response measured by measured by Lugano 2014 Classification

End point type

Secondary

End point timeframe

Up to approximately 37 months

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	27	15	3	5	0 ^[10]	6
Units: Months
median (confidence interval 95%)	5.4 (2.9 to 11.00)	3.0 (2.8 to 10.2)	2.8 (2.8 to 9999)	9999 (2.9 to 9999)	( to )	3.4 (1.6 to 9999)

Notes
[10] - DOR for Cohort E is evaluated using IMWG criteria and is presented separately.

No statistical analyses for this end point

Secondary: Duration of Response (DOR) as assessed by 2016 IMWG Response Criteria (Cohort E)

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End point title

Duration of Response (DOR) as assessed by 2016 IMWG Response Criteria (Cohort E)

End point description

DOR is defined as the time from CR or PR to documented disease progression or death. DOR for Cohort E was measured by the 2016 IMWG Response Criteria with response criteria defined as participants with either a sCR, CR, VGPR, or PR. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum Mprotein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. Cohorts A-D and F were presented in a previous outcome measure. The analysis population included all participants who have received at least one dose of study intervention and had a response measured by measured by 2016 IMWG Response Criteria.

End point type

Secondary

End point timeframe

Up to approximately 37 months

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	0 ^[11]	0 ^[12]	0 ^[13]	0 ^[14]	0 ^[15]	0 ^[16]
Units: Months
median (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )	( to )

Notes
[11] - DOR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[12] - DOR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[13] - DOR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[14] - DOR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[15] - Cohort E had no participants with a response.
[16] - DOR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)

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End point title

Disease Control Rate (DCR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)

End point description

DCR is % of participants who had tumor response per response criteria or have stable disease (SD) for ≥ 12 weeks before any evidence of progressive disease (PD). CR or PR were evaluated with CT and PET-CT. CR: complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤5 cm in longest transverse diameter of a lesion) and no new lesions. PR: partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% in length beyond normal). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Analysis population = all participants who have received at least 1 dose of study intervention and were evaluated using Lugano 2014 Classification.

End point type

Secondary

End point timeframe

Up to approximately 37 months

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	42	42	20	30	0 ^[17]	32
Units: Percentage of Participants
number (confidence interval 95%)	73.8 (58.0 to 86.1)	59.5 (43.3 to 74.4)	25.0 (8.7 to 49.1)	16.7 (5.6 to 34.7)	( to )	31.3 (16.1 to 50.0)

Notes
[17] - DCR for Cohort E is evaluated using IMWG criteria and is presented separately.

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) as Assessed by 2016 IMWG Response Criteria (Cohort E)

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End point title

Disease Control Rate (DCR) as Assessed by 2016 IMWG Response Criteria (Cohort E)

End point description

DCR is % of participants who achieved tumor response or have SD for ≥12 weeks before any evidence of PD. Response criteria: either a sCR, CR, VGPR, or PR. CR: negative immunofixation of serum and urine & disappearance of any soft tissue plasmacytomas & <5% plasmacytomas in the bone marrow; sCR: CR as above + normal serum FLC assay ratio and absence of clonal cells in bone marrow; VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR: ≥50% reduction of serum Mprotein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. SD: Not meeting criteria for CR, VGPR, PR, or PD. PD as defined by prespecified 2016 IMWG response criteria. Cohorts A-D and F were presented in a previous outcome measure. Analysis population included all participants who have received at least one dose of study intervention and were evaluated using 2016 IMWG Response Criteria 2016.

End point type

Secondary

End point timeframe

Up to approximately 37 months

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	0 ^[18]	0 ^[19]	0 ^[20]	0 ^[21]	25	0 ^[22]
Units: Percentage of Participants
number (confidence interval 95%)	( to )	( to )	( to )	( to )	16.0 (4.5 to 36.1)	( to )

Notes
[18] - DCR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[19] - DCR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[20] - DCR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[21] - DCR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.
[22] - DCR for Cohorts A-D & F is evaluated using IWGC Lugano Classification and is presented separately.

No statistical analyses for this end point

Secondary: Lowest Plasma Concentration (Ctrough) of Vibostolimab

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End point title

Lowest Plasma Concentration (Ctrough) of Vibostolimab

End point description

Ctrough is the lowest concentration reached by a drug before the next dose is administered. Blood samples collected predose were used to determine Ctrough of Vibostolimab. The analysis population included all participants who received at least one dose of intervention and had data for the corresponding cycle.

End point type

Secondary

End point timeframe

Predose at Cycles 1, 3, 7, 11, 15, 19, 23, 27 and 31. Cycle = 3 weeks

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	35	40	18	18	25	25
Units: ug/mL
geometric mean (confidence interval 95%)
Cycle 1	8.06 (6.71 to 9.68)	9.86 (8.22 to 11.8)	10.0 (6.61 to 15.3)	9.64 (7.24 to 12.9)	9.86 (6.52 to 14.9)	9.52 (6.95 to 13.0)
Cycle 3	15.3 (12.4 to 18.8)	17.0 (13.3 to 21.6)	22.6 (13.5 to 38.0)	14.5 (7.55 to 27.9)	17.9 (5.07 to 63.3)	20.2 (15.8 to 25.9)
Cycle 7	21.0 (17.1 to 25.8)	19.5 (14.9 to 25.5)	38.1 (6.15 to 236)	25.8 (5.19 to 129)	9999 (9999 to 9999)	22.1 (14.1 to 34.7)
Cycle 11	22.6 (16.6 to 30.8)	24.2 (16.3 to 35.8)	28.9 (0.251 to 3330)	40.7 (40.1 to 41.4)	9999 (9999 to 9999)	9999 (9999 to 9999)
Cycle 15	26.2 (17.0 to 40.6)	25.6 (17.4 to 37.8)	9999 (9999 to 9999)	40.6 (7.65 to 216)	9999 (9999 to 9999)	9999 (9999 to 9999)
Cycle 19	34.8 (21.6 to 56.2)	24.2 (13.8 to 42.6)	9999 (9999 to 9999)	31.1 (5.49 to 176)	9999 (9999 to 9999)	9999 (9999 to 9999)
Cycle 23	36.5 (24.2 to 55.2)	24.8 (15.2 to 40.3)	9999 (9999 to 9999)	51.5 (-9999 to 9999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Cycle 27	40.6 (22.8 to 72.4)	19.3 (9.23 to 40.4)	9999 (9999 to 9999)	48.9 (8.42 to 284)	9999 (9999 to 9999)	9999 (9999 to 9999)
Cycle 31	31.7 (2.43 to 413)	31.6 (6.13 to 163)	9999 (9999 to 9999)	38.0 (1.57 to 923)	9999 (9999 to 9999)	9999 (9999 to 9999)

No statistical analyses for this end point

Secondary: Maximum Concentration (Cmax) of Vibostolimab

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End point title

Maximum Concentration (Cmax) of Vibostolimab

End point description

Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected post dose were used to determine Cmax of Vibostolimab. The analysis population included all participants who received at least one dose of intervention and had data for the corresponding cycle.

End point type

Secondary

End point timeframe

Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks

End point values	Cohort A Pembrolizumab/vibostolimab coformulation	Cohort B Pembrolizumab/vibostolimab coformulation	Cohort C Pembrolizumab/vibostolimab coformulation	Cohort D Pembrolizumab/vibostolimab coformulation	Cohort E Pembrolizumab/vibostolimab coformulation	Cohort F Pembrolizumab/vibostolimab coformulation
Number of subjects analysed	37	38	17	26	24	28
Units: ug/mL
geometric mean (confidence interval 95%)
Cycle 1	85.8 (65.4 to 113)	85.4 (70.0 to 104)	42.6 (35.2 to 51.5)	64.2 (54.2 to 76.1)	53.2 (45.7 to 61.9)	55.2 (44.2 to 69.0)
Cycle 8	84.8 (69.9 to 103)	75.8 (61.5 to 93.5)	112 (22.8 to 552)	77.4 (46.4 to 129)	9999 (9999 to 9999)	80.9 (58.4 to 112)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to ~37 months.

Adverse event reporting additional description

All-cause mortality: All allocated participants. Safety: All allocated participants who received at least 1 dose of study intervention. Per protocol, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.1

Reporting group title

COHORT A

Reporting group description

Participants with classic Hodgkin’s lymphoma (cHL) or primary mediastinal B‐cell lymphoma (PMBCL) who are relapsed or refractory to at least 1 line of prior therapy (cHL) of at least 2 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

COHORT B

Reporting group description

Participants with cHL or PMBCL who are relapsed or refractory to at least 2 lines of prior therapies (cHL) of at least 3 lines of prior therapies (PMBCL) received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

COHORT E

Reporting group description

Participants with relapsed or refractory multiple myeloma (MM) following at least 3 lines of therapy and have exhausted all approved lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

COHORT D

Reporting group description

Participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

COHORT F

Reporting group description

Participants with relapsed or refractory non-Hodgkin’s lymphoma (NHL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Reporting group title

COHORT C

Reporting group description

Participants with relapsed or refractory follicular lymphoma (FL) following at least 2 lines of therapy received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.

Serious adverse events	COHORT A	COHORT B	COHORT E	COHORT D	COHORT F	COHORT C
Total subjects affected by serious adverse events
subjects affected / exposed	17 / 42 (40.48%)	11 / 42 (26.19%)	8 / 25 (32.00%)	11 / 30 (36.67%)	13 / 32 (40.63%)	8 / 20 (40.00%)
number of deaths (all causes)	14	10	14	24	15	9
number of deaths resulting from adverse events	2	2	0	4	3	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
High-grade B-cell lymphoma
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Leydig cell tumour of the testis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Squamous cell carcinoma
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Vascular disorders
Embolism
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Pyrexia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	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
Immune system disorders
Infusion related hypersensitivity reaction
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytokine release syndrome
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Oesophagobronchial fistula
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Pneumonitis
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	2 / 2	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
Respiratory failure
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	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 / 1
Investigations
Platelet count decreased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Pyloric stenosis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute cardiac event
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Myocarditis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure acute
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Atrial fibrillation
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Nervous system disorders
Seizure
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurotoxicity
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Neurological symptom
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Anaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Lymphadenopathy
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Thrombocytopenia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Dyspepsia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Gastric haemorrhage
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated gastritis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Oesophageal haemorrhage
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0
Nausea
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug eruption
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Rash
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Urticaria
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	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
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	2 / 32 (6.25%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Hydronephrosis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Nephritis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	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
Urinary retention
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Thyroiditis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscular weakness
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Myositis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Acute hepatitis B
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Aspergillus infection
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	2 / 20 (10.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	1 / 32 (3.13%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
Cellulitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	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
Encephalitis
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 2	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
Device related infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Gastroenteritis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Parainfluenzae virus infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	2 / 25 (8.00%)	0 / 30 (0.00%)	2 / 32 (6.25%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
Post-acute COVID-19 syndrome
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Sepsis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Upper respiratory tract infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Vascular device infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	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
Hypercalcaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	2 / 30 (6.67%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0

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

Non-serious adverse events	COHORT A	COHORT B	COHORT E	COHORT D	COHORT F	COHORT C
Total subjects affected by non serious adverse events
subjects affected / exposed	35 / 42 (83.33%)	39 / 42 (92.86%)	16 / 25 (64.00%)	21 / 30 (70.00%)	24 / 32 (75.00%)	15 / 20 (75.00%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	1 / 25 (4.00%)	1 / 30 (3.33%)	2 / 32 (6.25%)	1 / 20 (5.00%)
occurrences all number	0	1	3	1	2	1
General disorders and administration site conditions
Chills
subjects affected / exposed	1 / 42 (2.38%)	4 / 42 (9.52%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	2 / 20 (10.00%)
occurrences all number	1	4	1	0	0	2
Hyperthermia
subjects affected / exposed	3 / 42 (7.14%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	3	0	0	0	0	0
Fatigue
subjects affected / exposed	3 / 42 (7.14%)	6 / 42 (14.29%)	4 / 25 (16.00%)	2 / 30 (6.67%)	0 / 32 (0.00%)	1 / 20 (5.00%)
occurrences all number	3	6	4	2	0	1
Influenza like illness
subjects affected / exposed	3 / 42 (7.14%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	0	0	0	0	0
Pyrexia
subjects affected / exposed	8 / 42 (19.05%)	7 / 42 (16.67%)	3 / 25 (12.00%)	4 / 30 (13.33%)	4 / 32 (12.50%)	0 / 20 (0.00%)
occurrences all number	8	10	4	8	6	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 42 (9.52%)	2 / 42 (4.76%)	2 / 25 (8.00%)	1 / 30 (3.33%)	4 / 32 (12.50%)	1 / 20 (5.00%)
occurrences all number	4	2	2	1	4	1
Pneumonitis
subjects affected / exposed	3 / 42 (7.14%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	5	0	0	0	1	0
Rhinorrhoea
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	2 / 32 (6.25%)	0 / 20 (0.00%)
occurrences all number	1	0	1	0	2	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	3 / 25 (12.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	3	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	4 / 42 (9.52%)	1 / 42 (2.38%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	1	1	0	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	5 / 42 (11.90%)	3 / 42 (7.14%)	1 / 25 (4.00%)	2 / 30 (6.67%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	6	3	1	2	2	0
Alanine aminotransferase increased
subjects affected / exposed	5 / 42 (11.90%)	3 / 42 (7.14%)	2 / 25 (8.00%)	2 / 30 (6.67%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	5	3	2	4	1	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	3 / 42 (7.14%)	1 / 42 (2.38%)	1 / 25 (4.00%)	0 / 30 (0.00%)	4 / 32 (12.50%)	1 / 20 (5.00%)
occurrences all number	5	1	1	0	4	1
Blood creatinine increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	4 / 25 (16.00%)	3 / 30 (10.00%)	2 / 32 (6.25%)	1 / 20 (5.00%)
occurrences all number	0	0	4	3	2	1
Blood bilirubin increased
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	2 / 32 (6.25%)	0 / 20 (0.00%)
occurrences all number	5	0	0	0	2	0
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	3 / 25 (12.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	0	3	1	0	0
C-reactive protein increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	2 / 32 (6.25%)	0 / 20 (0.00%)
occurrences all number	0	0	0	1	2	0
Neutrophil count decreased
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 25 (0.00%)	2 / 30 (6.67%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	5	0	0	2	0	0
Lymphocyte count decreased
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	3 / 25 (12.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	0	4	0	0	0
Weight decreased
subjects affected / exposed	4 / 42 (9.52%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	0	1	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 42 (0.00%)	3 / 42 (7.14%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	3	1	0	0	2
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	3 / 42 (7.14%)	2 / 42 (4.76%)	1 / 25 (4.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	3	3	1	0	1	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	4	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	3 / 42 (7.14%)	4 / 42 (9.52%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	1 / 20 (5.00%)
occurrences all number	4	4	0	0	1	1
Dizziness
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0	1	0
Blood and lymphatic system disorders
Eosinophilia
subjects affected / exposed	3 / 42 (7.14%)	1 / 42 (2.38%)	2 / 25 (8.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	3	1	2	1	0	0
Neutropenia
subjects affected / exposed	4 / 42 (9.52%)	0 / 42 (0.00%)	1 / 25 (4.00%)	4 / 30 (13.33%)	5 / 32 (15.63%)	3 / 20 (15.00%)
occurrences all number	8	0	1	4	5	3
Thrombocytopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	3 / 25 (12.00%)	2 / 30 (6.67%)	4 / 32 (12.50%)	1 / 20 (5.00%)
occurrences all number	3	0	3	3	4	1
Anaemia
subjects affected / exposed	5 / 42 (11.90%)	5 / 42 (11.90%)	7 / 25 (28.00%)	5 / 30 (16.67%)	4 / 32 (12.50%)	1 / 20 (5.00%)
occurrences all number	7	6	8	5	5	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	7 / 42 (16.67%)	4 / 42 (9.52%)	0 / 25 (0.00%)	4 / 30 (13.33%)	3 / 32 (9.38%)	0 / 20 (0.00%)
occurrences all number	7	5	0	4	3	0
Nausea
subjects affected / exposed	4 / 42 (9.52%)	1 / 42 (2.38%)	2 / 25 (8.00%)	0 / 30 (0.00%)	5 / 32 (15.63%)	2 / 20 (10.00%)
occurrences all number	4	1	2	0	5	2
Vomiting
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	2 / 32 (6.25%)	0 / 20 (0.00%)
occurrences all number	1	0	1	0	2	0
Constipation
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	1 / 25 (4.00%)	1 / 30 (3.33%)	2 / 32 (6.25%)	2 / 20 (10.00%)
occurrences all number	2	2	2	1	3	2
Abdominal pain upper
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 25 (0.00%)	0 / 30 (0.00%)	2 / 32 (6.25%)	1 / 20 (5.00%)
occurrences all number	0	1	0	0	2	1
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 42 (2.38%)	5 / 42 (11.90%)	0 / 25 (0.00%)	2 / 30 (6.67%)	3 / 32 (9.38%)	1 / 20 (5.00%)
occurrences all number	1	5	0	2	3	1
Eczema
subjects affected / exposed	1 / 42 (2.38%)	3 / 42 (7.14%)	0 / 25 (0.00%)	1 / 30 (3.33%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	1	3	0	1	1	0
Pruritus
subjects affected / exposed	13 / 42 (30.95%)	8 / 42 (19.05%)	1 / 25 (4.00%)	2 / 30 (6.67%)	7 / 32 (21.88%)	1 / 20 (5.00%)
occurrences all number	14	13	1	2	7	1
Rash maculo-papular
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	0 / 25 (0.00%)	1 / 30 (3.33%)	1 / 32 (3.13%)	2 / 20 (10.00%)
occurrences all number	2	2	0	1	1	2
Endocrine disorders
Hypothyroidism
subjects affected / exposed	8 / 42 (19.05%)	3 / 42 (7.14%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	13	3	0	1	0	0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	4 / 42 (9.52%)	0 / 42 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	0	0	0	0	0
Bone pain
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0	1	0
Back pain
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	2 / 25 (8.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	2 / 20 (10.00%)
occurrences all number	3	2	2	1	0	2
Arthralgia
subjects affected / exposed	3 / 42 (7.14%)	2 / 42 (4.76%)	2 / 25 (8.00%)	1 / 30 (3.33%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	3	3	3	1	1	0
Muscular weakness
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	4 / 42 (9.52%)	7 / 42 (16.67%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 32 (0.00%)	2 / 20 (10.00%)
occurrences all number	4	8	0	1	0	2
Pneumonia
subjects affected / exposed	1 / 42 (2.38%)	3 / 42 (7.14%)	0 / 25 (0.00%)	2 / 30 (6.67%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	1	3	0	2	1	0
Urinary tract infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 25 (8.00%)	1 / 30 (3.33%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	0	0	2	1	1	0
Upper respiratory tract infection
subjects affected / exposed	6 / 42 (14.29%)	3 / 42 (7.14%)	3 / 25 (12.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	7	3	5	0	1	0
Metabolism and nutrition disorders
Hypercalcaemia
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	4 / 25 (16.00%)	2 / 30 (6.67%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	3	4	3	0	0
Decreased appetite
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	4 / 25 (16.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	3	2	4	0	1	0
Hyperglycaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 25 (4.00%)	1 / 30 (3.33%)	3 / 32 (9.38%)	1 / 20 (5.00%)
occurrences all number	0	0	2	1	3	1
Hypernatraemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 32 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	3 / 25 (12.00%)	0 / 30 (0.00%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	0	0	3	0	1	0
Hypokalaemia
subjects affected / exposed	1 / 42 (2.38%)	4 / 42 (9.52%)	0 / 25 (0.00%)	2 / 30 (6.67%)	1 / 32 (3.13%)	0 / 20 (0.00%)
occurrences all number	2	5	0	2	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

13 Oct 2021

Amendment 2: To incorporate changes requested by various country Health Authorities (Germany, Spain, France, and Denmark)

04 Mar 2022

Amendment 3: Addition of an inclusion criterion pertaining to prior use of brentuximab vedotin in Cohort B participants with cHL in Germany-specific requirements per the Federal Institute for Drugs and Medical Devices (BfArM) request. In addition, added an exception for participants in Cohort E who are unable to receive all regionally approved therapies as part of their prior lines of treatment. Minor discrepancies were corrected for clarification.

29 Aug 2022

Amendment 4: Merck Sharp & Dohme Corp. underwent an entity name and address change to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted only in an entity name change and update to the address.

16 Feb 2024

Amendment 5: To redefine the end of the study language, because the study primary objective has been met and additional data are not required.

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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