Trial Outcomes & Findings for Study of First-line Pembrolizumab (MK-3475) With Lenvatinib (MK-7902/E7080) in Urothelial Carcinoma Cisplatin-ineligible Participants Whose Tumors Express Programmed Cell Death-Ligand 1 and in Participants Ineligible for Platinum-containing Chemotherapy (MK-7902-011/E7080-G000-317/ LEAP-011) (NCT NCT03898180)

Last Updated: 2026-02-05

Results Overview

PFS was defined as the time from randomization to the first documented PD per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

505 participants

Primary outcome timeframe

Up to approximately 25 months

Results posted on

2026-02-05

Participant Flow

Per protocol, response/progression or adverse events (AEs) that occurred during the second course of pembrolizumab were not included in efficacy or safety outcome measures.

Participant milestones

Participant milestones
Measure	Pembrolizumab + Lenvatinib Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease (PD) or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab + lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed complete response (CR) initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab + placebo arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Overall Study STARTED	251	254
Overall Study Treated	247	254
Overall Study Pembrolizumab + Lenvatinib vs. Pembrolizumab + Placebo Efficacy Analyses	245	242
Overall Study Pembrolizumab + Lenvatinib vs. Pembrolizumab + Placebo Safety Analyses	241	242
Overall Study Received Second Course of Pembrolizumab	2	5
Overall Study COMPLETED	63	77
Overall Study NOT COMPLETED	188	177

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab + Lenvatinib Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease (PD) or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab + lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed complete response (CR) initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab + placebo arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Overall Study Death	178	173
Overall Study Physician Decision	1	0
Overall Study Sponsor Decision	3	0
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	5	4

Baseline Characteristics

Study of First-line Pembrolizumab (MK-3475) With Lenvatinib (MK-7902/E7080) in Urothelial Carcinoma Cisplatin-ineligible Participants Whose Tumors Express Programmed Cell Death-Ligand 1 and in Participants Ineligible for Platinum-containing Chemotherapy (MK-7902-011/E7080-G000-317/ LEAP-011)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + Lenvatinib n=251 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab + lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=254 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab + placebo arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Total n=505 Participants Total of all reporting groups
Age, Continuous	72.3 Years STANDARD_DEVIATION 9.3 • n=25 Participants	71.9 Years STANDARD_DEVIATION 8.5 • n=26 Participants	72.1 Years STANDARD_DEVIATION 8.9 • n=51 Participants
Sex: Female, Male Female	77 Participants n=25 Participants	59 Participants n=26 Participants	136 Participants n=51 Participants
Sex: Female, Male Male	174 Participants n=25 Participants	195 Participants n=26 Participants	369 Participants n=51 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=25 Participants	10 Participants n=26 Participants	27 Participants n=51 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	213 Participants n=25 Participants	218 Participants n=26 Participants	431 Participants n=51 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	21 Participants n=25 Participants	26 Participants n=26 Participants	47 Participants n=51 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants	1 Participants n=26 Participants	1 Participants n=51 Participants
Race (NIH/OMB) Asian	78 Participants n=25 Participants	79 Participants n=26 Participants	157 Participants n=51 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants
Race (NIH/OMB) Black or African American	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants
Race (NIH/OMB) White	164 Participants n=25 Participants	157 Participants n=26 Participants	321 Participants n=51 Participants
Race (NIH/OMB) More than one race	0 Participants n=25 Participants	1 Participants n=26 Participants	1 Participants n=51 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=25 Participants	16 Participants n=26 Participants	25 Participants n=51 Participants
Chemotherapy Ineligibility, Combined Positive Score (CPS), Eastern Cooperative Oncology Group (ECOG) Ineligible for any platinum agents CPS ≥10 ECOG 2	83 Participants n=25 Participants	84 Participants n=26 Participants	167 Participants n=51 Participants
Chemotherapy Ineligibility, Combined Positive Score (CPS), Eastern Cooperative Oncology Group (ECOG) Ineligible for any platinum agents CPS <10 ECOG 2	118 Participants n=25 Participants	120 Participants n=26 Participants	238 Participants n=51 Participants
Chemotherapy Ineligibility, Combined Positive Score (CPS), Eastern Cooperative Oncology Group (ECOG) Cisplatin-ineligible CPS ≥10 ECOG 2	8 Participants n=25 Participants	8 Participants n=26 Participants	16 Participants n=51 Participants
Chemotherapy Ineligibility, Combined Positive Score (CPS), Eastern Cooperative Oncology Group (ECOG) Cisplatin-ineligible CPS ≥10 ECOG 0 or 1	42 Participants n=25 Participants	42 Participants n=26 Participants	84 Participants n=51 Participants

PRIMARY outcome

Timeframe: Up to approximately 25 months

Population: All participants randomized prior to the protocol-specified primary completion analysis data cut-off.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=245 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=242 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Progression-free Survival (PFS)	4.5 Months Interval 4.0 to 6.0	4.0 Months Interval 2.7 to 5.4

PRIMARY outcome

Timeframe: Up to approximately 25 months

Population: All participants randomized prior to the protocol-specified primary completion analysis data cut-off.

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=245 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=242 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Overall Survival (OS)	11.8 Months Interval 9.1 to 15.1	12.9 Months Interval 9.8 to 17.8

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All participants randomized prior to the protocol-specified primary completion analysis data cut-off.

ORR was defined as the percentage of participants who had a confirmed CR (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. The percentage of participants who experienced a CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=245 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=242 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Objective Response Rate (ORR)	33.1 Percentage of Participants Interval 27.2 to 39.3	28.9 Percentage of Participants Interval 23.3 to 35.1

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All participants randomized prior to the protocol-specified primary completion analysis data cut-off and who also experienced a confirmed CR or partial response.

For participants who demonstrated a confirmed CR (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions as well as an absolute increase of ≥5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR per RECIST 1.1 for participants who experienced a confirmed CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=81 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=70 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Duration of Response (DOR)	NA Months NA = Median, upper limit and lower limit of range could not be reached at time of data cut-off due to insufficient number of responding participants with relapse.	NA Months NA = Median, upper limit and lower limit of range could not be reached at time of data cut-off due to insufficient number of responding participants with relapse.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All participants randomized prior to the protocol-specified primary completion analysis data cut-off.

DCR was defined as the percentage of participants who have a CR (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD \[PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD\]). DCR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. The DCR as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=245 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=242 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Disease Control Rate (DCR)	66.9 Percentage of Participants Interval 60.7 to 72.8	56.2 Percentage of Participants Interval 49.7 to 62.5

SECONDARY outcome

Timeframe: Baseline and Week 11

Population: All participants who were randomized and received at least one dose of study treatment prior to the primary completion analysis data cut-off and who also had data available from at least 1 EORTC QLQ-C30 Item 29 and 30 assessment.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding GHS ("How would you rate your overall health during the past week?") and QOL ("How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QOL (EORTC QLQ-C30 Item 30) combined score is presented. A higher score indicates a better outcome. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021, as specified in the Supplemental Statistical Analysis Plan (sSAP).

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=240 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=231 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS) (Item 29) and Quality of Life (QOL) (Item 30) Combined Score	0.73 Scores on a scale Interval -2.63 to 4.09	3.79 Scores on a scale Interval 0.47 to 7.12

SECONDARY outcome

Timeframe: Baseline and up to approximately 25 months

Population: All participants who were randomized and received at least one dose of study treatment prior to the primary completion analysis data cut-off and who also had data available from baseline and ≥1 post-baseline EORTC QLQ-C30 Item 29 and 30 assessments.

TTD was defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) \& QOL (EORTC QLQ-C30 Item 30) combined score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding GHS ("How would you rate your overall health during the past week?") and QOL ("How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QOL combined score, is presented. A longer TTD indicates a better outcome. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021, as specified in the sSAP.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=233 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=226 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS (Item 29) and QOL (Item 30) Combined Score	3.4 Months Interval 2.1 to 4.3	7.6 Months Interval 4.2 to NA = Upper limit was not reached at time of data cut-off due to an insufficient number of participants having the first onset of a ≥10-point negative change (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) \& QOL (EORTC QLQ-C30 Item 30) combined score.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All participants who were randomized and received at least one dose of study treatment prior to the primary completion analysis data cut-off.

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=241 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=242 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Number of Participants Who Experience an AE	234 Participants	235 Participants

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All participants who were randomized and received at least one dose of study treatment prior to the primary completion analysis data cut-off.

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=241 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Pembrolizumab + Placebo n=242 Participants Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo. At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab or who had stopped pembrolizumab due to confirmed CR initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Number of Participants Who Discontinue Study Treatment Due to an AE	83 Participants	44 Participants

Adverse Events

Lenvatinib + Pembrolizumab First Course

Serious events: 155 serious events

Other events: 238 other events

Deaths: 178 deaths

Placebo + Pembrolizumab First Course

Serious events: 116 serious events

Other events: 236 other events

Deaths: 175 deaths

Lenvatinib + Pembrolizumab → Pembrolizumab Second Course

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo + Pembrolizumab → Pembrolizumab Second Course

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Lenvatinib + Pembrolizumab First Course n=247 participants at risk Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib.	Placebo + Pembrolizumab First Course n=254 participants at risk Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo.	Lenvatinib + Pembrolizumab → Pembrolizumab Second Course n=2 participants at risk At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Placebo + Pembrolizumab → Pembrolizumab Second Course n=5 participants at risk At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Blood and lymphatic system disorders Anaemia	1.2% 3/247 • Number of events 3 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	2.4% 6/254 • Number of events 6 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Blood and lymphatic system disorders Febrile neutropenia	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Acute coronary syndrome	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Atrial fibrillation	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Atrial flutter	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Cardiac arrest	1.6% 4/247 • Number of events 4 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Cardiac failure	2.0% 5/247 • Number of events 5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Cardiopulmonary failure	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Coronary artery disease	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Myocardial infarction	0.81% 2/247 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.79% 2/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Prinzmetal angina	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Tachycardia	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Cardiac disorders Ventricular tachycardia	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Ear and labyrinth disorders Vertigo	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Endocrine disorders Hyperthyroidism	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Endocrine disorders Hypophysitis	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.79% 2/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Endocrine disorders Hypothyroidism	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Abdominal pain	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Anal fistula	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Colitis	1.2% 3/247 • Number of events 3 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	1.2% 3/254 • Number of events 3 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Colitis microscopic	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Constipation	0.81% 2/247 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Diarrhoea	1.6% 4/247 • Number of events 5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Diverticular perforation	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Dysphagia	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Enterovesical fistula	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.79% 2/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Gastric ulcer	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Ileus	1.6% 4/247 • Number of events 4 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Immune-mediated enterocolitis	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Inguinal hernia	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Intestinal fistula	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Intestinal haemorrhage	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Intestinal obstruction	0.81% 2/247 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Large intestinal haemorrhage	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Mechanical ileus	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.

Other adverse events
Measure	Lenvatinib + Pembrolizumab First Course n=247 participants at risk Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued lenvatinib.	Placebo + Pembrolizumab First Course n=254 participants at risk Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until PD or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinued placebo.	Lenvatinib + Pembrolizumab → Pembrolizumab Second Course n=2 participants at risk At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS lenvatinib arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.	Placebo + Pembrolizumab → Pembrolizumab Second Course n=5 participants at risk At the investigator's discretion, eligible participants randomized to the pembrolizumab PLUS placebo arm who completed the first course of pembrolizumab, or who had stopped pembrolizumab due to confirmed CR, initiated a second course of pembrolizumab (200 mg IV infusion on Day 1 of each 21-day cycle, for up to 17 cycles \[up to approximately 1 additional year\]) upon experiencing PD.
Blood and lymphatic system disorders Anaemia	19.4% 48/247 • Number of events 57 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	25.2% 64/254 • Number of events 74 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Endocrine disorders Hyperthyroidism	6.5% 16/247 • Number of events 17 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	4.7% 12/254 • Number of events 13 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Endocrine disorders Hypothyroidism	39.7% 98/247 • Number of events 109 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	10.6% 27/254 • Number of events 30 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Eye disorders Xerophthalmia	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Abdominal pain	10.1% 25/247 • Number of events 32 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	9.1% 23/254 • Number of events 26 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Abdominal pain upper	5.7% 14/247 • Number of events 17 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	4.3% 11/254 • Number of events 12 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Constipation	16.2% 40/247 • Number of events 50 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	15.0% 38/254 • Number of events 45 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Diarrhoea	26.3% 65/247 • Number of events 111 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.1% 51/254 • Number of events 75 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Haemorrhoids	2.4% 6/247 • Number of events 6 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.79% 2/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	50.0% 1/2 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Nausea	21.1% 52/247 • Number of events 65 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	17.3% 44/254 • Number of events 53 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Stomatitis	7.3% 18/247 • Number of events 23 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	2.8% 7/254 • Number of events 10 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Gastrointestinal disorders Vomiting	15.0% 37/247 • Number of events 42 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	10.2% 26/254 • Number of events 31 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
General disorders Asthenia	21.1% 52/247 • Number of events 62 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	13.0% 33/254 • Number of events 46 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
General disorders Fatigue	21.1% 52/247 • Number of events 58 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.9% 53/254 • Number of events 55 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
General disorders Mucosal inflammation	8.1% 20/247 • Number of events 21 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	3.5% 9/254 • Number of events 9 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
General disorders Oedema peripheral	11.3% 28/247 • Number of events 31 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	10.2% 26/254 • Number of events 27 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
General disorders Pyrexia	10.1% 25/247 • Number of events 33 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	13.8% 35/254 • Number of events 47 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Infections and infestations Cystitis	1.2% 3/247 • Number of events 3 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	3.1% 8/254 • Number of events 9 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Infections and infestations Gastrointestinal infection	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Infections and infestations Upper respiratory tract infection	3.2% 8/247 • Number of events 8 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	2.8% 7/254 • Number of events 10 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Infections and infestations Urinary tract infection	21.9% 54/247 • Number of events 75 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	18.1% 46/254 • Number of events 66 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	40.0% 2/5 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/247 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Alanine aminotransferase increased	8.9% 22/247 • Number of events 29 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	5.9% 15/254 • Number of events 19 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Amylase increased	9.7% 24/247 • Number of events 33 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	10.6% 27/254 • Number of events 39 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Aspartate aminotransferase increased	8.5% 21/247 • Number of events 25 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	6.7% 17/254 • Number of events 20 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Blood alkaline phosphatase increased	7.7% 19/247 • Number of events 21 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	6.3% 16/254 • Number of events 16 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Blood creatine phosphokinase increased	1.6% 4/247 • Number of events 5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	4.3% 11/254 • Number of events 16 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	40.0% 2/5 • Number of events 5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Blood creatinine increased	11.3% 28/247 • Number of events 33 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	7.5% 19/254 • Number of events 27 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Blood urea increased	0.81% 2/247 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Lipase increased	15.8% 39/247 • Number of events 49 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	11.0% 28/254 • Number of events 40 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Platelet count decreased	6.5% 16/247 • Number of events 23 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	2.8% 7/254 • Number of events 10 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Investigations Weight decreased	20.2% 50/247 • Number of events 51 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	9.1% 23/254 • Number of events 24 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Decreased appetite	27.5% 68/247 • Number of events 85 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	16.9% 43/254 • Number of events 51 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Hypercholesterolaemia	1.2% 3/247 • Number of events 3 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/254 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Hyperglycaemia	4.9% 12/247 • Number of events 12 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	4.7% 12/254 • Number of events 15 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Hyperkalaemia	3.6% 9/247 • Number of events 12 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	6.3% 16/254 • Number of events 18 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Hypoalbuminaemia	7.7% 19/247 • Number of events 22 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	4.7% 12/254 • Number of events 12 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Hyponatraemia	7.3% 18/247 • Number of events 21 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	6.7% 17/254 • Number of events 19 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.40% 1/247 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.39% 1/254 • Number of events 2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	20.0% 1/5 • Number of events 1 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.
Musculoskeletal and connective tissue disorders Arthralgia	10.9% 27/247 • Number of events 38 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	10.2% 26/254 • Number of events 31 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/2 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.	0.00% 0/5 • Up to approximately 52 months All-Cause Mortality (ACM) includes all randomized participants. AEs include all randomized participants who received ≥1 dose of study treatment. Progression of the cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. Data are reported by treatment received. ACM and AEs are reported separately for pembrolizumab second course.