Trial Outcomes & Findings for Study of Pembrolizumab (MK-3475) in Participants With Advanced Urothelial Cancer (MK-3475-052/KEYNOTE-052) (NCT NCT02335424)

Last Updated: 2023-03-02

Results Overview

ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

374 participants

Primary outcome timeframe

Up to approximately 80.5 months

Results posted on

2023-03-02

Participant Flow

Participants were eligible to receive second course treatment with pembrolizumab if they met criteria for re-treatment. Per protocol, only data generated during the initial course of treatment contributed to efficacy and safety outcome measures.

Results are based on a database cutoff date of 18-February-2022.

Participant milestones

Participant milestones
Measure	Pembrolizumab 200 mg Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Study STARTED	374
Overall Study Treated	370
Overall Study Received Second Course Treatment	13
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	374

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab 200 mg Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Study Withdrawal by Subject	19
Overall Study Adverse Event	25
Overall Study Death	273
Overall Study Lost to Follow-up	3
Overall Study Physician Decision	13
Overall Study Participation in study terminated by Sponsor	39
Overall Study Protocol Violation	1
Overall Study Screen failure	1

Baseline Characteristics

Study of Pembrolizumab (MK-3475) in Participants With Advanced Urothelial Cancer (MK-3475-052/KEYNOTE-052)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab 200 mg n=374 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Age, Continuous	73.0 Years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants
Sex: Female, Male Male	288 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	326 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	26 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	332 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants	28.9 Percentage of participants Interval 24.3 to 33.8

PRIMARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS

ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	32.6 Percentage of participants Interval 27.2 to 38.4

PRIMARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS

ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	47.3 Percentage of participants Interval 37.7 to 57.0

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and who had a confirmed CR or confirmed PR.

DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=107 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants	33.4 Months Interval 18.2 to 48.7

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment, had a PD-L1 positive expression of ≥1% CPS, and who had a confirmed CR or PR.

DOR was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=92 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	35.8 Months Interval 20.4 to NA = upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment, had a PD-L1 strong positive expression of ≥10% CPS, and who had a confirmed CR or PR.

DOR was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=52 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	NA Months Interval 18.1 to NA = median and upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment.

PFS was determined in all participants. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants	2.5 Months Interval 2.1 to 3.4

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.

PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	3.4 Months Interval 2.3 to 4.0

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.

PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	4.9 Months Interval 3.8 to 10.8

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment

OS was determined for all participants and was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival (OS) in All Participants	11.3 Months Interval 9.7 to 13.1

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.

OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	12.4 Months Interval 10.8 to 15.0

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.

OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	18.5 Months Interval 12.2 to 28.5

SECONDARY outcome

Timeframe: Month 6

Population: All participants who received at least one dose of study treatment during the initial course of treatment

The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants	34.0 Percentage of participants Interval 29.2 to 38.8

SECONDARY outcome

Timeframe: Month 6

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.

The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	37.9 Percentage of participants Interval 32.2 to 43.5

SECONDARY outcome

Timeframe: Month 6

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.

The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	49.0 Percentage of participants Interval 39.4 to 57.9

SECONDARY outcome

Timeframe: Month 12

Population: All participants who received at least one dose of study treatment during the initial course of treatment

The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants	22.9 Percentage of participants Interval 18.7 to 27.3

SECONDARY outcome

Timeframe: Month 12

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.

The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	25.8 Percentage of participants Interval 20.8 to 31.1

SECONDARY outcome

Timeframe: Month 12

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.

The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	38.6 Percentage of participants Interval 29.5 to 47.7

SECONDARY outcome

Timeframe: Month 6

Population: All participants who received at least one dose of study treatment during the initial course of treatment

The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival Rate (OS Rate) at Month 6 in All Participants	67.0 Percentage of participants Interval 62.0 to 71.5

SECONDARY outcome

Timeframe: Month 6

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.

The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	71.3 Percentage of participants Interval 65.6 to 76.2

SECONDARY outcome

Timeframe: Month 6

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.

The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	76.3 Percentage of participants Interval 67.2 to 83.2

SECONDARY outcome

Timeframe: Month 12

Population: All participants who received at least one dose of study treatment during the initial course of treatment

The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival Rate (OS Rate) at Month 12 in All Participants	46.9 Percentage of participants Interval 41.8 to 51.9

SECONDARY outcome

Timeframe: Month 12

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.

The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	50.9 Percentage of participants Interval 45.0 to 56.6

SECONDARY outcome

Timeframe: Month 12

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.

The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	60.7 Percentage of participants Interval 50.9 to 69.1

SECONDARY outcome

Timeframe: Day 1

Population: All participants who received at least one dose of study treatment during the initial course of treatment

PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of \<1% = negative; ≥1% = positive; and ≥10% = strongly positive. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Programmed Cell Death Ligand 1 (PD-L1) Expression Status PD-L1 CPS <1%	79 Participants
Programmed Cell Death Ligand 1 (PD-L1) Expression Status PD-L1 CPS ≥1% to <10%	172 Participants
Programmed Cell Death Ligand 1 (PD-L1) Expression Status PD-L1 CPS ≥10%	110 Participants
Programmed Cell Death Ligand 1 (PD-L1) Expression Status Unknown	9 Participants

SECONDARY outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Number of Participants Who Experienced At Least One Adverse Event (AE)	361 Participants

SECONDARY outcome

Timeframe: Up to approximately 26 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)	62 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment during the initial course of treatment

ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=370 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants	30.5 Percentage of participants Interval 25.9 to 35.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS

ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=282 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%	34.4 Percentage of participants Interval 28.9 to 40.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approximately 80.5 months

Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥10% CPS

ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.

Outcome measures

Outcome measures
Measure	Pembrolizumab 200 mg n=110 Participants Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%	49.1 Percentage of participants Interval 39.4 to 58.8

Adverse Events

Pembrolizumab

Serious events: 190 serious events

Other events: 342 other events

Deaths: 305 deaths

Second Course Pembrolizumab

Serious events: 6 serious events

Other events: 12 other events

Deaths: 8 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 The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pembrolizumab n=370 participants at risk Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.	Second Course Pembrolizumab n=13 participants at risk Participants who met the criteria for retreatment received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle for up to 1 year of treatment.
Infections and infestations Renal abscess	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pyelonephritis acute	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Anaemia	1.6% 6/370 • Number of events 6 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Febrile neutropenia	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Immune thrombocytopenia	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Acute left ventricular failure	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Acute myocardial infarction	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Angina pectoris	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Atrial fibrillation	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Atrioventricular block	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Ischaemic cardiomyopathy	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Myocardial infarction	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Myocarditis	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Pericarditis	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Supraventricular tachycardia	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Addison's disease	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Adrenal insufficiency	1.4% 5/370 • Number of events 5 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypophysitis	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypopituitarism	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Thyroiditis	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Ascites	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Colitis	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	1.1% 4/370 • Number of events 4 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	1.4% 5/370 • Number of events 5 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Duodenal obstruction	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Gastrointestinal motility disorder	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Ileus	0.81% 3/370 • Number of events 3 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Intestinal ischaemia	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Intestinal obstruction	0.81% 3/370 • Number of events 3 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Large intestinal obstruction	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Large intestine perforation	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Pancreatitis acute	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Proctitis	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Rectal haemorrhage	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Small intestinal obstruction	0.81% 3/370 • Number of events 3 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Asthenia	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Cardiac complication associated with device	0.27% 1/370 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.

Other adverse events
Measure	Pembrolizumab n=370 participants at risk Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year.	Second Course Pembrolizumab n=13 participants at risk Participants who met the criteria for retreatment received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle for up to 1 year of treatment.
Blood and lymphatic system disorders Anaemia	19.7% 73/370 • Number of events 84 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	23.1% 3/13 • Number of events 3 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Ear and labyrinth disorders Ear swelling	0.00% 0/370 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypothyroidism	11.4% 42/370 • Number of events 42 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Eye disorders Diplopia	0.00% 0/370 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	12.7% 47/370 • Number of events 57 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain lower	1.6% 6/370 • Number of events 6 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Ascites	0.00% 0/370 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	23.5% 87/370 • Number of events 100 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	23.1% 3/13 • Number of events 3 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	22.2% 82/370 • Number of events 121 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Dry mouth	6.2% 23/370 • Number of events 23 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	20.8% 77/370 • Number of events 89 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	15.1% 56/370 • Number of events 79 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Asthenia	11.9% 44/370 • Number of events 49 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Chest pain	5.4% 20/370 • Number of events 22 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Chills	7.3% 27/370 • Number of events 31 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Fatigue	34.9% 129/370 • Number of events 156 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Influenza like illness	5.1% 19/370 • Number of events 21 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Oedema	1.6% 6/370 • Number of events 6 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Oedema peripheral	17.0% 63/370 • Number of events 74 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Peripheral swelling	1.9% 7/370 • Number of events 7 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
General disorders Pyrexia	13.8% 51/370 • Number of events 64 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Hepatobiliary disorders Hepatitis acute	0.00% 0/370 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Nasopharyngitis	4.3% 16/370 • Number of events 17 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Tooth infection	0.54% 2/370 • Number of events 3 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Upper respiratory tract infection	5.1% 19/370 • Number of events 23 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Urinary tract infection	20.5% 76/370 • Number of events 98 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Fall	5.9% 22/370 • Number of events 26 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Stoma site haemorrhage	0.00% 0/370 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations Alanine aminotransferase increased	7.3% 27/370 • Number of events 31 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations Aspartate aminotransferase increased	7.3% 27/370 • Number of events 31 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood alkaline phosphatase increased	7.3% 27/370 • Number of events 30 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood creatinine increased	14.3% 53/370 • Number of events 67 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations Inspiratory capacity decreased	0.00% 0/370 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations Weight decreased	11.9% 44/370 • Number of events 47 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	15.4% 2/13 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Investigations White blood cell count decreased	0.54% 2/370 • Number of events 2 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Decreased appetite	27.6% 102/370 • Number of events 116 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Dehydration	5.1% 19/370 • Number of events 19 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyperglycaemia	10.0% 37/370 • Number of events 51 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyperkalaemia	6.5% 24/370 • Number of events 29 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	7.7% 1/13 • Number of events 1 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypoalbuminaemia	5.1% 19/370 • Number of events 26 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/13 • Up to approximately 80.5 months Adverse events=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" \& "Disease progression" not related to study drug are excluded as AEs.