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Clinical Trial Results:
A Phase II, Open-label, Single-arm, Multicenter Study to Evaluate Efficacy and Safety of Pembrolizumab Monotherapy in Subjects with Advanced Recurrent Ovarian Cancer (KEYNOTE-100)

Summary
EudraCT number	2015-003338-29
Trial protocol	SE ES LT DE FI NO BE NL FR PL GB IT
Global end of trial date	18 Mar 2021

Results information
Results version number	v1(current)
This version publication date	13 Mar 2022
First version publication date	13 Mar 2022
Other versions

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

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Trial information

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Sponsor protocol code

3475-100

ISRCTN number

US NCT number

NCT02674061

WHO universal trial number (UTN)

Other trial identifiers

JAPIC-CTI: 163237

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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

18 Mar 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

18 Sep 2019

Global end of trial reached?

Yes

Global end of trial date

18 Mar 2021

Was the trial ended prematurely?

Main objective of the trial

This study will assess the efficacy and safety of pembrolizumab (MK-3475) monotherapy in female participants with recurrent ovarian cancer (ROC) who have received up to 5 prior lines of treatment including platinum-based treatment for ROC (1 to 6 total prior lines counting front line therapy). Participants will be enrolled into two separate cohorts based on the number of prior lines of treatment received for ROC.

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

25 Feb 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 15

Country: Number of subjects enrolled

Belgium: 7

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

Finland: 9

Country: Number of subjects enrolled

France: 21

Country: Number of subjects enrolled

Germany: 22

Country: Number of subjects enrolled

Israel: 29

Country: Number of subjects enrolled

Italy: 44

Country: Number of subjects enrolled

Japan: 21

Country: Number of subjects enrolled

Lithuania: 10

Country: Number of subjects enrolled

Netherlands: 23

Country: Number of subjects enrolled

Norway: 13

Country: Number of subjects enrolled

Poland: 5

Country: Number of subjects enrolled

Russian Federation: 27

Country: Number of subjects enrolled

South Africa: 7

Country: Number of subjects enrolled

Spain: 23

Country: Number of subjects enrolled

Sweden: 5

Country: Number of subjects enrolled

United Kingdom: 17

Country: Number of subjects enrolled

United States: 64

Worldwide total number of subjects

376

EEA total number of subjects

182

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)

236

From 65 to 84 years

138

85 years and over

Subject disposition

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Recruitment details

Per protocol, Progression-free survival by Blinded Independent Central Review, Overall Survival, adverse events in all participants from end of trial database (cutoff 18-Mar-2021). Objective Response Rate, Duration of Response, Disease Control Rate, safety outcomes, sub-group analyses of PFS and OS from final analysis database (cutoff 18-Sep-2019).

Screening details

Seven participants (Cohorts A=5; B = 2) received a second course of pembrolizumab at the investigator's discretion per protocol. Response/progression or adverse events (AEs) that occurred during second course of pembrolizumab were not counted towards efficacy or safety outcome measures.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort A: Pembrolizumab

Arm description

Participants in Cohort A received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Arm type

Experimental

Investigational medicinal product name

pembrolizumab

Investigational medicinal product code

Other name

MK-3475 KEYTRUDA®

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle

Cohort B: Pembrolizumab

Arm description

Participants in Cohort B received 3-5 prior lines of treatment for ROC (4-6 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Arm type

Experimental

Investigational medicinal product name

pembrolizumab

Investigational medicinal product code

Other name

MK-3475 KEYTRUDA®

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle

Number of subjects in period 1	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Started	285	91
Completed	0	0
Not completed	285	91
Consent withdrawn by subject	9	1
Death	229	77
Participation in study discontinued by Sponsor	44	10
Lost to follow-up	3	3

Baseline characteristics

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Reporting group title

Cohort A: Pembrolizumab

Reporting group description

Reporting group title

Cohort B: Pembrolizumab

Reporting group description

Reporting group values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab	Total
Number of subjects	285	91	376
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	174	62	236
From 65-84 years	109	29	138
85 years and over	2	0	2
Age Continuous
Units: Years
arithmetic mean (standard deviation)	60.5 ( 11.3 )	59.5 ( 9.9 )	-
Sex: Female, Male
Units: Participants
Female	285	91	376
Male	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	27	3	30
Native Hawaiian or Other Pacific Islander	0	1	1
Black or African American	4	1	5
White	253	85	338
More than one race	1	0	1
Unknown or Not Reported	0	1	1
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	6	3	9
Not Hispanic or Latino	258	85	343
Unknown or Not Reported	21	3	24

End points

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Reporting group title

Cohort A: Pembrolizumab

Reporting group description

Reporting group title

Cohort B: Pembrolizumab

Reporting group description

Subject analysis set title

Cohort A Participants with PD-L1 CPS ≥1

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort A with Programmed Cell Death Ligand-1 (PD-L1) Combined Positive Score (CPS) ≥1 received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Subject analysis set title

Cohort B Participants with PD-L1 CPS ≥1

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort B with PD-L1 CPS ≥1 received 3-5 prior lines of treatment for ROC (4-6 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Subject analysis set title

Cohort A Participants with PD-L1 CPS ≥10

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort A with PD-L1 CPS ≥10 received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Subject analysis set title

Cohort B Participants with PD-L1 CPS ≥10

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort B with PD-L1 CPS ≥10 received 3-5 prior lines of treatment for ROC (4-6 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Subject analysis set title

Cohort A Participants with PFI/TFI ≥3-6 Months

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort A with a platinum-free interval (PFI)/treatment-free interval (TFI) ≥3-6 Months (based on last regimen received) received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Subject analysis set title

Cohort A Participants with PFI/TFI >6-12 Months

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort A with a platinum-free interval (PFI)/treatment-free interval (TFI) >6-12 Months (based on last regimen received) received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and were administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to ~1 additional year).

Primary: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in all Cohort A and Cohort B Participants

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End point title

Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in all Cohort A and Cohort B Participants ^[1]

End point description

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters [SOD] of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Primary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

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: There were no statistical analyses planned for this endpoint.

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of participants
number (confidence interval 95%)	8.1 (5.2 to 11.9)	9.9 (4.6 to 17.9)

No statistical analyses for this end point

Primary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with Programmed Cell Death Ligand-1 (PD-L1) Combined Positive Score (CPS) ≥10

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End point title

ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with Programmed Cell Death Ligand-1 (PD-L1) Combined Positive Score (CPS) ≥10 ^[2]

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥10 and received ≥1 dose of study drug.

End point type

Primary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

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: There were no statistical analyses planned for this endpoint.

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of participants
number (confidence interval 95%)	11.6 (3.9 to 25.1)	18.2 (5.2 to 40.3)

No statistical analyses for this end point

Primary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1 ^[3]

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Primary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

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: There were no statistical analyses planned for this endpoint.

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of participants
number (confidence interval 95%)	6.9 (2.8 to 13.8)	10.2 (3.4 to 22.2)

No statistical analyses for this end point

Secondary: Duration of Response (DOR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

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End point title

Duration of Response (DOR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until progressive disease (PD) or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by Kaplan-Meier (KM) method and reported as Median DOR with a full range. The analysis population included all participants in Cohort A and Cohort B who had a confirmed CR or PR per RECIST 1.1 by BICR and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	23	9
Units: Months
median (full range (min-max))	8.3 (3.9 to 35.4)	23.6 (3.3 to 32.8)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. A value of 9999=Median and upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10, had a confirmed CR or PR per RECIST 1.1 by BICR, and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	5	4
Units: Months
median (full range (min-max))	11.1 (8.3 to 20.5)	9999 (5.9 to 9999)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. A value of 9999=Median and upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1, had a confirmed CR or PR per RECIST 1.1 by BICR, and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	7	5
Units: Months
median (full range (min-max))	11.1 (8.2 to 35.4)	9999 (5.9 to 9999)

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

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End point title

Disease Control Rate (DCR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

End point description

DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or Stable Disease (SD: Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or Non-CR/Non-PD (NN: does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	22.1 (17.4 to 27.4)	22.0 (14.0 to 31.9)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	25.6 (13.5 to 41.2)	31.8 (13.9 to 54.9)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of participants
number (confidence interval 95%)	24.8 (16.7 to 34.3)	22.4 (11.8 to 36.6)

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

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End point title

Progression Free Survival (PFS) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by BICR with a 95% confidence interval (CI). The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~58.8 months (through database cut-off date of 18-March-2021)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.2)	2.1 (2.1 to 2.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	23.0 (18.1 to 28.1)	27.2 (18.2 to 36.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	10.5 (7.0 to 14.8)	13.1 (6.5 to 22.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	5.8 (3.2 to 9.5)	13.1 (6.5 to 22.2)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by BICR with a 95% CI. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 4.2)	2.1 (2.0 to 8.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	26.9 (14.4 to 41.2)	36.8 (17.0 to 57.0)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	18.2 (7.9 to 31.9)	16.8 (3.5 to 38.7)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	9.1 (2.4 to 21.3)	16.8 (3.5 to 38.7)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by BICR with a 95% CI. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.8)	2.1 (2.1 to 3.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	25.5 (17.2 to 34.5)	25.6 (14.1 to 38.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	16.4 (9.5 to 25.0)	11.6 (3.8 to 24.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	9.0 (3.9 to 16.7)	11.6 (3.8 to 24.4)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

ORR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator. The analysis population included all participants in Cohort A and Cohort B that received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of participants
number (confidence interval 95%)	7.0 (4.3 to 10.6)	8.8 (3.9 to 16.6)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of participants
number (confidence interval 95%)	11.6 (3.9 to 25.1)	18.2 (5.2 to 40.3)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of participants
number (confidence interval 95%)	6.9 (2.8 to 13.8)	12.2 (4.6 to 24.8)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

DOR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. The analysis population included all participants in Cohort A and Cohort B who had a confirmed CR or PR per RECIST 1.1 by investigator and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	20	8
Units: Months
median (full range (min-max))	9.1 (4.0 to 35.4)	7.5 (4.2 to 32.9)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10, had a confirmed CR or PR per RECIST 1.1 by investigator, and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	5	4
Units: Months
median (full range (min-max))	9.8 (4.0 to 22.6)	7.3 (4.2 to 32.9)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method and reported as Median DOR with a full range. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1, had confirmed CR or PR per RECIST 1.1 by investigator, and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	7	6
Units: Months
median (full range (min-max))	9.8 (4.0 to 35.4)	7.5 (4.2 to 32.9)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

DCR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	24.9 (20.0 to 30.4)	17.6 (10.4 to 27.0)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	25.6 (13.5 to 41.2)	27.3 (10.7 to 50.2)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of participants
number (confidence interval 95%)	24.8 (16.7 to 34.3)	20.4 (10.2 to 34.3)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

PFS per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by investigator with a 95% CI. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.1)	2.1 (2.1 to 2.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	24.0 (19.2 to 29.1)	17.8 (10.7 to 26.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	7.7 (4.9 to 11.3)	6.7 (2.7 to 13.1)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported. The analysis population included all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	5.0 (2.8 to 8.3)	4.4 (1.4 to 10.1)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by investigator with a 95% CI. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 4.1)	2.2 (2.0 to 4.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	24.2 (12.5 to 38.1)	27.3 (11.1 to 46.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	10.8 (3.5 to 22.8)	13.6 (3.4 to 30.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	5.4 (1.0 to 15.8)	9.1 (1.6 to 25.1)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by investigator with a 95% CI. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.2)	2.1 (2.1 to 2.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	24.1 (16.2 to 32.9)	20.4 (10.5 to 32.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	11.0 (5.7 to 18.2)	10.2 (3.7 to 20.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	5.6 (1.9 to 12.3)	6.1 (1.6 to 15.2)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with Platinum-Free Interval (PFI)/Treatment-Free Interval (TFI) ≥3-6 Months

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End point title

ORR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with Platinum-Free Interval (PFI)/Treatment-Free Interval (TFI) ≥3-6 Months

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of ORR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of participants
number (confidence interval 95%)	7.9 (3.8 to 14.0)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/ TFI >6-12 Months

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End point title

ORR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/ TFI >6-12 Months

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of ORR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	8.7 (4.2 to 15.4)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

DOR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months, had a confirmed CR or PR per RECIST 1.1 by BICR, and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DOR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	10
Units: Months
median (full range (min-max))	8.3 (4.1 to 14.5)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

DOR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

For participants who demonstrated confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as a Median DOR with a full range. Per protocol PFI/TFI >6-12 months subgroup analysis of DOR per RECIST 1.1 by BICR was not planned or executed in Cohort B. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months, had a confirmed CR or PR per RECIST 1.1 by BICR, and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	10
Units: Months
median (full range (min-max))	4.7 (3.9 to 34.6)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

DCR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

DCR was defined as the percentage of participants in the analysis population who have a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DCR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of participants
number (confidence interval 95%)	18.9 (12.5 to 26.8)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

DCR per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

DCR was defined as the percentage of participants in the analysis population who have a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage to for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of DCR per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	21.7 (14.6 to 30.4)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

PFS per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as a Median PFS per RECIST 1.1 by BICR with a 95% CI. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.1)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	18.2 (11.9 to 25.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	6.4 (2.8 to 11.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	1.1 (0.1 to 5.2)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

PFS per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as Median PFS per RECIST 1.1 by investigator with a 95% CI. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	23.1 (15.7 to 31.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	12.0 (6.4 to 19.4)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/ TFI ≥3-6 Months

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End point title

ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/ TFI ≥3-6 Months

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of ORR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of participants
number (confidence interval 95%)	8.7 (4.4 to 15.0)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by BICR was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	8.0 (3.5 to 14.9)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months, had a confirmed CR or PR per RECIST 1.1 by BICR, and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DOR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	11
Units: Months
median (full range (min-max))	8.4 (5.0 to 17.2)

No statistical analyses for this end point

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/ TFI >6-12 Months

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End point title

ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/ TFI >6-12 Months

End point description

ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of ORR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	5.2 (1.9 to 11.0)

No statistical analyses for this end point

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

For participants who demonstrated confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn’t progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR was analyzed by KM method and reported as Median DOR with a full range. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months, had a confirmed CR or PR per RECIST 1.1 by BICR, and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of DOR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	6
Units: Months
median (full range (min-max))	9.7 (4.0 to 34.6)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (doesn’t qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DCR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of participants
number (confidence interval 95%)	21.3 (14.5 to 29.4)

No statistical analyses for this end point

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD]) or NN (doesn’t qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. DCR was analyzed by test of binomial parameter and reported as the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of DCR per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of participants
number (confidence interval 95%)	23.5 (16.1 to 32.3)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as a Median PFS per RECIST 1.1 by investigator with a 95% CI. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.1)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	20.5 (13.9 to 27.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	6.8 (3.2 to 12.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	4.0 (1.4 to 8.8)

No statistical analyses for this end point

Secondary: PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method and reported as a Median PFS per RECIST 1.1 by investigator with a 95% CI. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Months
median (confidence interval 95%)	2.1 (2.1 to 2.1)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	5.6 (2.3 to 10.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	22.6 (15.5 to 30.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by investigator was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	3.7 (1.2 to 8.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 6 in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with OS (OS Rate) at Month 6 in all Cohort A and Cohort B Participants

End point description

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	82.5 (77.5 to 86.4)	79.0 (69.0 to 86.0)

No statistical analyses for this end point

Secondary: Overall Survival (OS) in all Cohort A and Cohort B Participants

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End point title

Overall Survival (OS) in all Cohort A and Cohort B Participants

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. OS was analyzed by KM method and reported as Median OS with a 95% CI. The analysis population was all participants in Cohort A and Cohort B that received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~58.8 months (through database cut-off date of 18-March-2021)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Months
median (confidence interval 95%)	18.7 (17.0 to 22.4)	17.6 (13.3 to 24.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 12 in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with OS (OS Rate) at Month 12 in all Cohort A and Cohort B Participants

End point description

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	66.0 (60.1 to 71.1)	66.6 (55.8 to 75.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 18 in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with OS (OS Rate) at Month 18 in all Cohort A and Cohort B Participants

End point description

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	51.3 (45.4 to 57.0)	48.5 (37.8 to 58.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 24 in all Cohort A and Cohort B Participants

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End point title

Percentage of Participants with OS (OS Rate) at Month 24 in all Cohort A and Cohort B Participants

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 24 is reported. The analysis population was all participants in Cohort A and Cohort B that received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 24

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Percentage of Participants
number (confidence interval 95%)	40.5 (34.7 to 46.1)	40.6 (30.4 to 50.6)

No statistical analyses for this end point

Secondary: OS in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

OS in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. OS was analyzed by KM method and is reported as Median OS with a 95% CI. A value of 9999 = Based on the statistical model used for data analysis, upper limit of 95% CI was not reached by the data cut-off date. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Months
median (confidence interval 95%)	21.9 (12.9 to 26.8)	24.0 (14.5 to 9999)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	81.0 (65.6 to 90.0)	95.5 (71.9 to 99.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	69.1 (52.8 to 80.7)	86.4 (63.4 to 95.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

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End point title

Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PD-L1 CPS ≥10	Cohort B Participants with PD-L1 CPS ≥10
Number of subjects analysed	43	22
Units: Percentage of Participants
number (confidence interval 95%)	54.3 (38.1 to 67.9)	59.1 (36.1 to 76.2)

No statistical analyses for this end point

Secondary: OS in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

OS in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. OS was analyzed by KM method and is reported as Median OS with a 95% CI. The analysis population included a subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Months
median (confidence interval 95%)	20.6 (15.2 to 23.2)	20.7 (13.6 to 27.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	80.0 (70.8 to 86.6)	87.8 (74.8 to 94.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	65.0 (54.8 to 73.5)	75.5 (60.9 to 85.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

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End point title

Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

End point description

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PD-L1 CPS ≥1	Cohort B Participants with PD-L1 CPS ≥1
Number of subjects analysed	101	49
Units: Percentage of Participants
number (confidence interval 95%)	52.6 (42.4 to 61.9)	53.1 (38.3 to 65.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI >3-6 months subgroup analysis of OS rate at Month 6 was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	77.7 (69.4 to 84.1)

No statistical analyses for this end point

Secondary: OS in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

OS in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. OS was analyzed by KM method and is reported as Median OS with a 95% CI. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Months
median (confidence interval 95%)	17.2 (14.0 to 20.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI >3-6 months subgroup analysis of OS rate at Month 12 was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	62.5 (53.4 to 70.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

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End point title

Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants with PFI/TFI ≥3-6 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months and received ≥1 dose of study drug. Per protocol PFI/TFI >3-6 months subgroup analysis of OS rate at Month 18 was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PFI/TFI ≥3-6 Months
Number of subjects analysed	127
Units: Percentage of Participants
number (confidence interval 95%)	45.2 (36.3 to 53.8)

No statistical analyses for this end point

Secondary: OS in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

OS in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. OS was analyzed by KM method and is reported as Median OS with a 95% CI. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of OS was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Up to ~43 months (through database cut-off date of 18-September-2019)

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Months
median (confidence interval 95%)	22.1 (15.2 to 27.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of OS rate at Month 6 was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	86.1 (78.3 to 91.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of OS rate at Month 18 was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 18

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	54.6 (45.0 to 63.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

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End point title

Percentage of Participants with OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants with PFI/TFI >6-12 Months

End point description

OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported. The analysis population included a subgroup of participants in Cohort A who had a PFI/TFI (duration from end of treatment to disease recurrence) >6-12 months and received ≥1 dose of study drug. Per protocol PFI/TFI >6-12 months subgroup analysis of OS rate at Month 12 was not planned or executed in Cohort B.

End point type

Secondary

End point timeframe

Month 12

End point values	Cohort A Participants with PFI/TFI >6-12 Months
Number of subjects analysed	115
Units: Percentage of Participants
number (confidence interval 95%)	68.7 (59.3 to 76.3)

No statistical analyses for this end point

Secondary: Number of Participants Who Experienced an Adverse Event (AE)

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End point title

Number of Participants Who Experienced an Adverse Event (AE)

End point description

An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be 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 pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. As specified by the protocol, the number of participants who experienced at least one AE is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~58.8 months (through database cut-off date of 18-March-2021)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Participants	274	85

No statistical analyses for this end point

Secondary: Number of Participants Who Discontinued Study Treatment due to an AE

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End point title

Number of Participants Who Discontinued Study Treatment due to an AE

End point description

An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be 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 pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. As specified by the protocol, the number of participants who discontinued study treatment due to an AE is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Up to ~58.8 months (through database cut-off date of 18-March-2021)

End point values	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab
Number of subjects analysed	285	91
Units: Participants	23	4

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to approximately 58.8 months (based on the database cut-off date of 18-March-2021)

Adverse event reporting additional description

All participants who received ≥1 dose of study drug. Per protocol, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression (NP)", "Malignant NP" and "Disease progression" considered not related to study drug are excluded as AEs. Second course pembrolizumab AEs are presented separately per protocol.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Cohort A: Pembrolizumab

Reporting group description

Reporting group title

Cohort B: Pembrolizumab

Reporting group description

Reporting group title

Cohort A: Second Course Pembrolizumab

Reporting group description

Eligible participants in Cohort A who stopped pembrolizumab with stable disease (SD) or better but progressed after stopping study treatment initiated a second course of pembrolizumab at the investigator's discretion at the same dose and schedule (200 mg Q3W) for up to 17 cycles (up to approximately 1 additional year).

Reporting group title

Cohort B: Second Course Pembrolizumab

Reporting group description

Eligible participants in Cohort B who stopped pembrolizumab with SD or better but progressed after stopping study treatment initiated a second course of pembrolizumab at the investigator's discretion at the same dose and schedule (200 mg Q3W) for up to 17 cycles (up to approximately 1 additional year).

Serious adverse events	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab	Cohort A: Second Course Pembrolizumab	Cohort B: Second Course Pembrolizumab
Total subjects affected by serious adverse events
subjects affected / exposed	91 / 285 (31.93%)	26 / 91 (28.57%)	1 / 5 (20.00%)	0 / 2 (0.00%)
number of deaths (all causes)	233	77	1	0
number of deaths resulting from adverse events	2	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infected neoplasm
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Malignant ascites
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Paraneoplastic syndrome
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour associated fever
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Circulatory collapse
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vena cava embolism
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vena cava thrombosis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incarcerated hernia
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sarcoidosis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Female genital tract fistula
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	3 / 285 (1.05%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	7 / 285 (2.46%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 8	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	3 / 285 (1.05%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Dyspnoea at rest
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood sodium decreased
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Gastrointestinal injury
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral infarction
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intercostal neuralgia
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myasthenic syndrome
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Splenic haematoma
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	9 / 285 (3.16%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 12	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune colitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	3 / 285 (1.05%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	3 / 3	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colonic fistula
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 285 (1.05%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal perforation
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	5 / 285 (1.75%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	4 / 285 (1.40%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intussusception
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal haemorrhage
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal ulcer
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	2 / 285 (0.70%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	10 / 285 (3.51%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 14	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	2 / 285 (0.70%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	3 / 285 (1.05%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Budd-Chiari syndrome
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Portal vein thrombosis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Biliary obstruction
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perivascular dermatitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stevens-Johnson syndrome
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 285 (0.70%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydroureter
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Addison's disease
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Adrenal insufficiency
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoaldosteronism
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
Hypophysitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypothyroidism
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphocytic hypophysitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Acinetobacter infection
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Herpes virus infection
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis streptococcal
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural infection bacterial
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	4 / 285 (1.40%)	1 / 91 (1.10%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	2 / 5	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis syndrome
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 285 (0.35%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	3 / 285 (1.05%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 285 (0.35%)	0 / 91 (0.00%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	1 / 285 (0.35%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cohort A: Pembrolizumab	Cohort B: Pembrolizumab	Cohort A: Second Course Pembrolizumab	Cohort B: Second Course Pembrolizumab
Total subjects affected by non serious adverse events
subjects affected / exposed	272 / 285 (95.44%)	84 / 91 (92.31%)	5 / 5 (100.00%)	2 / 2 (100.00%)
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	45 / 285 (15.79%)	26 / 91 (28.57%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	52	29	0	0
Fatigue
subjects affected / exposed	96 / 285 (33.68%)	22 / 91 (24.18%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	118	27	2	0
Oedema peripheral
subjects affected / exposed	22 / 285 (7.72%)	4 / 91 (4.40%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	30	4	0	0
Pain
subjects affected / exposed	2 / 285 (0.70%)	5 / 91 (5.49%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	2	5	0	0
Pyrexia
subjects affected / exposed	31 / 285 (10.88%)	9 / 91 (9.89%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	37	11	0	0
Hernia
subjects affected / exposed	0 / 285 (0.00%)	1 / 91 (1.10%)	0 / 5 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	1	0	1
Suprapubic pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	38 / 285 (13.33%)	13 / 91 (14.29%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	44	14	0	0
Dyspnoea
subjects affected / exposed	40 / 285 (14.04%)	6 / 91 (6.59%)	0 / 5 (0.00%)	1 / 2 (50.00%)
occurrences all number	49	8	0	1
Haemoptysis
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	2	0
Productive cough
subjects affected / exposed	7 / 285 (2.46%)	1 / 91 (1.10%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	8	1	1	0
Sputum discoloured
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Psychiatric disorders
Insomnia
subjects affected / exposed	17 / 285 (5.96%)	3 / 91 (3.30%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	19	4	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	17 / 285 (5.96%)	1 / 91 (1.10%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	19	1	1	0
Aspartate aminotransferase increased
subjects affected / exposed	19 / 285 (6.67%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	21	2	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	19 / 285 (6.67%)	3 / 91 (3.30%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	23	3	1	0
Weight decreased
subjects affected / exposed	17 / 285 (5.96%)	6 / 91 (6.59%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	17	6	0	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Blood bicarbonate increased
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Blood lactate dehydrogenase increased
subjects affected / exposed	7 / 285 (2.46%)	1 / 91 (1.10%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	7	1	1	0
PCO2 increased
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
White blood cells urine positive
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Injury, poisoning and procedural complications
Bone contusion
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Incision site complication
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	21 / 285 (7.37%)	6 / 91 (6.59%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	22	6	0	0
Headache
subjects affected / exposed	25 / 285 (8.77%)	9 / 91 (9.89%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	32	11	2	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	40 / 285 (14.04%)	13 / 91 (14.29%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	58	18	0	0
Lymph node pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Eye disorders
Eyelid rash
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	3	0
Eyelids pruritus
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	0	0	3	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	20 / 285 (7.02%)	5 / 91 (5.49%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	24	5	2	0
Abdominal pain
subjects affected / exposed	76 / 285 (26.67%)	20 / 91 (21.98%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	90	26	0	0
Abdominal pain upper
subjects affected / exposed	17 / 285 (5.96%)	8 / 91 (8.79%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	19	9	0	0
Ascites
subjects affected / exposed	31 / 285 (10.88%)	7 / 91 (7.69%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	47	7	0	0
Constipation
subjects affected / exposed	59 / 285 (20.70%)	22 / 91 (24.18%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	63	25	0	0
Diarrhoea
subjects affected / exposed	56 / 285 (19.65%)	20 / 91 (21.98%)	2 / 5 (40.00%)	0 / 2 (0.00%)
occurrences all number	85	30	2	0
Dry mouth
subjects affected / exposed	15 / 285 (5.26%)	2 / 91 (2.20%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	15	2	0	0
Dyspepsia
subjects affected / exposed	18 / 285 (6.32%)	1 / 91 (1.10%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	19	1	0	0
Nausea
subjects affected / exposed	95 / 285 (33.33%)	24 / 91 (26.37%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	123	30	2	0
Stomatitis
subjects affected / exposed	14 / 285 (4.91%)	5 / 91 (5.49%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	15	5	0	0
Vomiting
subjects affected / exposed	61 / 285 (21.40%)	18 / 91 (19.78%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	78	24	0	0
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	15 / 285 (5.26%)	3 / 91 (3.30%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	15	3	0	0
Pruritus
subjects affected / exposed	31 / 285 (10.88%)	12 / 91 (13.19%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	35	16	0	0
Rash
subjects affected / exposed	27 / 285 (9.47%)	8 / 91 (8.79%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	32	11	0	0
Rash maculo-papular
subjects affected / exposed	10 / 285 (3.51%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	13	0	1	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	5 / 285 (1.75%)	5 / 91 (5.49%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	5	5	0	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	19 / 285 (6.67%)	7 / 91 (7.69%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	20	7	0	0
Hypothyroidism
subjects affected / exposed	33 / 285 (11.58%)	11 / 91 (12.09%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	33	14	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	30 / 285 (10.53%)	14 / 91 (15.38%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	33	23	1	0
Back pain
subjects affected / exposed	25 / 285 (8.77%)	10 / 91 (10.99%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	28	14	0	0
Muscle spasms
subjects affected / exposed	8 / 285 (2.81%)	5 / 91 (5.49%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	9	5	0	0
Myalgia
subjects affected / exposed	19 / 285 (6.67%)	5 / 91 (5.49%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	20	5	0	0
Pain in extremity
subjects affected / exposed	14 / 285 (4.91%)	7 / 91 (7.69%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	19	8	0	0
Groin pain
subjects affected / exposed	3 / 285 (1.05%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	3	0	2	0
Muscular weakness
subjects affected / exposed	3 / 285 (1.05%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	3	0	1	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	16 / 285 (5.61%)	5 / 91 (5.49%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	20	6	0	0
Urinary tract infection
subjects affected / exposed	21 / 285 (7.37%)	10 / 91 (10.99%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	26	13	0	0
COVID-19
subjects affected / exposed	0 / 285 (0.00%)	0 / 91 (0.00%)	0 / 5 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	1
Sinusitis
subjects affected / exposed	4 / 285 (1.40%)	2 / 91 (2.20%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	4	2	1	0
Upper respiratory tract infection
subjects affected / exposed	11 / 285 (3.86%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	12	0	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	76 / 285 (26.67%)	14 / 91 (15.38%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	84	16	0	0
Hypomagnesaemia
subjects affected / exposed	7 / 285 (2.46%)	6 / 91 (6.59%)	0 / 5 (0.00%)	0 / 2 (0.00%)
occurrences all number	7	8	0	0
Hyponatraemia
subjects affected / exposed	10 / 285 (3.51%)	0 / 91 (0.00%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	11	0	4	0
Hypophosphataemia
subjects affected / exposed	4 / 285 (1.40%)	2 / 91 (2.20%)	1 / 5 (20.00%)	0 / 2 (0.00%)
occurrences all number	5	6	2	0

More information

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Were there any global substantial amendments to the protocol? Yes

19 Jan 2018

Amendment 1 expanded on biomarker cutpoint language to provide maximum flexibility to perform additional data analysis, updated language related to pharmacokinetics (PK), and revised guidelines for immune-related adverse events.

21 Feb 2020

Amendment 2 added standard pembrolizumab extension study language.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase II, Open-label, Single-arm, Multicenter Study to Evaluate Efficacy and Safety of Pembrolizumab Monotherapy in Subjects with Advanced Recurrent Ovarian Cancer (KEYNOTE-100)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in all Cohort A and Cohort B Participants

Primary: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in all Cohort A and Cohort B Participants

Primary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with Programmed Cell Death Ligand-1 (PD-L1) Combined Positive Score (CPS) ≥10

Primary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with Programmed Cell Death Ligand-1 (PD-L1) Combined Positive Score (CPS) ≥10

Primary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Primary: ORR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Duration of Response (DOR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Duration of Response (DOR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: DOR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Disease Control Rate (DCR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Disease Control Rate (DCR) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: DCR per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Progression Free Survival (PFS) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Progression Free Survival (PFS) per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in all Cohort A and Cohort B Participants

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: PFS per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: ORR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: ORR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: ORR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: DOR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: DOR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: DOR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: DCR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: DCR per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: DCR per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥1

Secondary: PFS per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: PFS per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: Percentage of Participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by Investigator in all Cohort A and Cohort B Participants

Secondary: PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Secondary: PFS per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants with PD-L1 CPS ≥10

Clinical Trial Results:
A Phase II, Open-label, Single-arm, Multicenter Study to Evaluate Efficacy and Safety of Pembrolizumab Monotherapy in Subjects with Advanced Recurrent Ovarian Cancer (KEYNOTE-100)