Trial Outcomes & Findings for Biomarkers of Response to Pembrolizumab Combined With Chemotherapy in Non-Small Cell Lung Cancer (KEYNOTE-782, MK-3475-782) (NCT NCT03664024)

NCT ID: NCT03664024

Last Updated: 2024-08-22

Results Overview

Objective response rate is the proportion of participants who have a confirmed complete response (CR) or partial response (PR). Objective response rate is assessed by investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with missing data are considered non-responders. The percentage of participants with an ORR is presented.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 118 participants
• Primary outcome timeframe: Up to ~25 months
• Results posted on: 2024-08-22

Participant Flow

Participant milestones

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.
Overall Study STARTED	118
Overall Study Treated	117
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	118

Reasons for withdrawal

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.
Overall Study Follow-up discontinued by sponsor	34
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	2
Overall Study Death	80

Baseline Characteristics

Biomarkers of Response to Pembrolizumab Combined With Chemotherapy in Non-Small Cell Lung Cancer (KEYNOTE-782, MK-3475-782)

Baseline characteristics by cohort

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=118 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.
Age, Continuous	64.5 Years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	116 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	2 Participants n=5 Participants
Race (NIH/OMB) White	114 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to ~25 months

Population: All participants who received at least one dose of study intervention.

Objective response rate is the proportion of participants who have a confirmed complete response (CR) or partial response (PR). Objective response rate is assessed by investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with missing data are considered non-responders. The percentage of participants with an ORR is presented.

Outcome measures

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=117 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.	Pembrolizumab Plus Platinum-doublet Chemotherapy Responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants in this arm were considered responders if they had a complete or partial response. This arm is a subset of the overall arm.	Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants were considered non-responders if they did not have complete or partial response. This arm is a subset of the overall arm.
Objective Response Rate	40.2 Percentage of Participants Interval 31.2 to 49.6	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1)

Population: All participants who received at least one dose of study intervention and had samples evaluable for ctDNA TMB analysis.

Cell-free ctDNA allows the exploration of tumor features from blood samples. TMB is a measure of mutational load in tumor cells and expressed as the number of somatic mutations per megabase (mut/MB) of DNA. The mean TMB in cell-free ctDNA of participants is presented.

Outcome measures

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=101 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.	Pembrolizumab Plus Platinum-doublet Chemotherapy Responder n=42 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants in this arm were considered responders if they had a complete or partial response. This arm is a subset of the overall arm.	Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder n=59 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants were considered non-responders if they did not have complete or partial response. This arm is a subset of the overall arm.
Tumor Mutation Burden (TMB) in Cell-free Circulating Tumor Deoxyribonucleic Acid (ctDNA)	9 Mut/MB Standard Deviation 11.6	8 Mut/MB Standard Deviation 8.3	10 Mut/MB Standard Deviation 13.5

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received at least one dose of study intervention.

PFS is defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first as assessed by investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The Kaplan-Meier estimate of median PFS using the product-limit (Kaplan-Meier) method for censored data is presented.

Outcome measures

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=117 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.	Pembrolizumab Plus Platinum-doublet Chemotherapy Responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants in this arm were considered responders if they had a complete or partial response. This arm is a subset of the overall arm.	Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants were considered non-responders if they did not have complete or partial response. This arm is a subset of the overall arm.
Progression Free Survival (PFS)	7.2 Months Interval 5.6 to 9.8	—	—

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received at least one dose of study intervention.

OS is defined as the time from the start of treatment to death due to any cause. The Kaplan-Meier estimate of median PFS using the product-limit (Kaplan-Meier) method for censored data is presented.

Outcome measures

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=117 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.	Pembrolizumab Plus Platinum-doublet Chemotherapy Responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants in this arm were considered responders if they had a complete or partial response. This arm is a subset of the overall arm.	Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants were considered non-responders if they did not have complete or partial response. This arm is a subset of the overall arm.
Overall Survival (OS)	18.1 Months Interval 13.5 to 25.6	—	—

SECONDARY outcome

Timeframe: Up to ~31 months

Population: All participants who received at least one dose of study intervention.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced an AE is presented.

Outcome measures

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=117 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.	Pembrolizumab Plus Platinum-doublet Chemotherapy Responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants in this arm were considered responders if they had a complete or partial response. This arm is a subset of the overall arm.	Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants were considered non-responders if they did not have complete or partial response. This arm is a subset of the overall arm.
Percentage of Participants Who Experienced One or More Adverse Events (AEs)	100 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Up to ~28 months

Population: All participants who received at least one dose of study intervention.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued the study intervention due to an AE is presented.

Outcome measures

Measure	Pembrolizumab Plus Platinum-doublet Chemotherapy n=117 Participants Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.	Pembrolizumab Plus Platinum-doublet Chemotherapy Responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants in this arm were considered responders if they had a complete or partial response. This arm is a subset of the overall arm.	Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years. Participants were considered non-responders if they did not have complete or partial response. This arm is a subset of the overall arm.
Percentage of Participants Discontinuing Study Intervention Due to an AE.	38.5 Percentage of Participants	—	—

Adverse Events

Pembrolizumab + Pemetrexed + Platinum Agent

Serious events: 60 serious events

Other events: 114 other events

Deaths: 80 deaths

Serious adverse events

Measure	Pembrolizumab + Pemetrexed + Platinum Agent n=117 participants at risk Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.
Blood and lymphatic system disorders Anaemia	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Febrile neutropenia	4.3% 5/117 • Number of events 5 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Neutropenia	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Pancytopenia	2.6% 3/117 • Number of events 3 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Thrombocytopenia	2.6% 3/117 • Number of events 3 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Cardiac arrest	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Cardio-respiratory arrest	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Cardiopulmonary failure	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Cardiotoxicity	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Myocarditis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Pericardial effusion	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Adrenal insufficiency	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Eye disorders Papilloedema	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	3.4% 4/117 • Number of events 4 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Dysphagia	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Gastric haemorrhage	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Haematemesis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Stomatitis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Death	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Fatigue	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders General physical health deterioration	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Pyrexia	1.7% 2/117 • Number of events 3 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Hepatobiliary disorders Immune-mediated hepatitis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Bronchitis	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Cellulitis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Device related bacteraemia	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Gangrene	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Haemophilus infection	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Influenza	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Lung abscess	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pneumonia	9.4% 11/117 • Number of events 13 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pulmonary sepsis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Respiratory tract infection	3.4% 4/117 • Number of events 5 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Sepsis	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Septic shock	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Upper respiratory tract infection	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Urinary tract infection	1.7% 2/117 • Number of events 3 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Femur fracture	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Tibia fracture	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Urinary tract stoma complication	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Troponin increased	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Dehydration	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Bone pain	0.85% 1/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Fracture malunion	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Pathological fracture	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Cerebral ischaemia	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Cerebrovascular accident	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Cognitive disorder	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Dizziness	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Hydrocephalus	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Seizure	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Vertebrobasilar insufficiency	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Psychiatric disorders Confusional state	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Acute kidney injury	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Tubulointerstitial nephritis	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.6% 3/117 • Number of events 4 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.7% 2/117 • Number of events 2 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.85% 1/117 • Number of events 1 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Other adverse events

Measure	Pembrolizumab + Pemetrexed + Platinum Agent n=117 participants at risk Participants received pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) on the first day of each 21-day cycle combined with a platinum-doublet of pemetrexed 500 mg/m\^2 IV infusion plus investigators choice of either carboplatin AUC 5 mg/mL/m or cisplatin 75 mg/m\^2 IV Q3W for up to 4 cycles, then pembrolizumab 200 mg plus pemetrexed 500 mg/m\^2 IV infusion for up to 31 additional cycles up to \~2 years.
Nervous system disorders Dizziness	8.5% 10/117 • Number of events 10 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Anaemia	61.5% 72/117 • Number of events 109 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Leukopenia	11.1% 13/117 • Number of events 16 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Neutropenia	24.8% 29/117 • Number of events 50 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Thrombocytopenia	14.5% 17/117 • Number of events 23 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hyperthyroidism	6.0% 7/117 • Number of events 8 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypothyroidism	12.0% 14/117 • Number of events 17 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Eye disorders Lacrimation increased	12.0% 14/117 • Number of events 14 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	17.9% 21/117 • Number of events 24 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	23.1% 27/117 • Number of events 44 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	30.8% 36/117 • Number of events 44 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	18.8% 22/117 • Number of events 27 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Asthenia	25.6% 30/117 • Number of events 46 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Chest pain	6.0% 7/117 • Number of events 9 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Fatigue	21.4% 25/117 • Number of events 39 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Mucosal inflammation	8.5% 10/117 • Number of events 10 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Oedema peripheral	13.7% 16/117 • Number of events 19 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Pyrexia	13.7% 16/117 • Number of events 25 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pneumonia	6.0% 7/117 • Number of events 7 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Urinary tract infection	11.1% 13/117 • Number of events 19 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Alanine aminotransferase increased	17.1% 20/117 • Number of events 32 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Amylase increased	7.7% 9/117 • Number of events 14 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Aspartate aminotransferase increased	15.4% 18/117 • Number of events 33 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood alkaline phosphatase increased	5.1% 6/117 • Number of events 7 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood creatinine increased	14.5% 17/117 • Number of events 30 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Gamma-glutamyltransferase increased	6.8% 8/117 • Number of events 10 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Neutrophil count decreased	6.0% 7/117 • Number of events 8 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Weight decreased	12.0% 14/117 • Number of events 14 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Decreased appetite	21.4% 25/117 • Number of events 26 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyperglycaemia	17.9% 21/117 • Number of events 25 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypokalaemia	6.8% 8/117 • Number of events 9 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypomagnesaemia	5.1% 6/117 • Number of events 7 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyponatraemia	7.7% 9/117 • Number of events 10 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypophosphataemia	5.1% 6/117 • Number of events 9 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Arthralgia	13.7% 16/117 • Number of events 22 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Back pain	10.3% 12/117 • Number of events 13 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Myalgia	5.1% 6/117 • Number of events 8 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Dysgeusia	6.0% 7/117 • Number of events 7 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Headache	7.7% 9/117 • Number of events 10 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Neuropathy peripheral	6.0% 7/117 • Number of events 7 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Renal impairment	7.7% 9/117 • Number of events 10 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Cough	10.3% 12/117 • Number of events 13 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.5% 17/117 • Number of events 20 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.0% 7/117 • Number of events 8 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Pruritus	5.1% 6/117 • Number of events 8 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Rash	6.0% 7/117 • Number of events 13 • For All-Cause Mortality: from allocation up to ~36 months. For AEs from start of treatment up to ~31 months. All-cause mortality: All allocated participants. Adverse events: All allocated participants who received at least 1 dose of study intervention. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp and Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.
• Publication restrictions are in place

Restriction type: OTHER