Trial Outcomes & Findings for Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151) (NCT NCT02821000)

NCT ID: NCT02821000

Last Updated: 2024-05-30

Results Overview

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can 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 is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 103 participants
• Primary outcome timeframe: Up to approximately 17 months (Through data cutoff date of 27-December-2017)
• Results posted on: 2024-05-30

Participant Flow

Participant milestones

Measure	Pembrolizumab Participants received pembrolizumab 2 mg/kg intravenous (IV) on Day 1 of each 21-day cycle. Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.
Overall Study STARTED	103
Overall Study Treated	103
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	103

Reasons for withdrawal

Measure	Pembrolizumab Participants received pembrolizumab 2 mg/kg intravenous (IV) on Day 1 of each 21-day cycle. Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.
Overall Study Death	89
Overall Study Sponsor Decision	12
Overall Study Withdrawal by Subject	2

Baseline Characteristics

All enrolled participants

Baseline characteristics by cohort

Measure	Pembrolizumab n=103 Participants Participants received pembrolizumab 2 mg/kg intravenous (IV) on Day 1 of each 21-day cycle. Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.
Age, Continuous	50.5 Years STANDARD_DEVIATION 14.2 • n=5 Participants • All enrolled participants
Sex: Female, Male Female	59 Participants n=5 Participants • All enrolled participants
Sex: Female, Male Male	44 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) Asian	103 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) White	0 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • All enrolled participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • All enrolled participants
Programmed Cell Death-Ligand 1 (PD-L1) Expression Status Positive for PD-L1	53 Participants n=5 Participants • All enrolled participants
Programmed Cell Death-Ligand 1 (PD-L1) Expression Status Negative for PD-L1	45 Participants n=5 Participants • All enrolled participants
Programmed Cell Death-Ligand 1 (PD-L1) Expression Status Unknown PD-L1 Status	5 Participants n=5 Participants • All enrolled participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=0	45 Participants n=5 Participants • All enrolled participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=1	58 Participants n=5 Participants • All enrolled participants
BRAF Mutation Expression Status Wild Type	82 Participants n=5 Participants • All enrolled participants
BRAF Mutation Expression Status Mutant	20 Participants n=5 Participants • All enrolled participants
BRAF Mutation Expression Status Unknown	1 Participants n=5 Participants • All enrolled participants

PRIMARY outcome

Timeframe: Up to approximately 17 months (Through data cutoff date of 27-December-2017)

Population: The safety population consisted of all participants who received at least one dose of study treatment.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can 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 is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.

Outcome measures

Measure	Pembrolizumab n=103 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Number of Participants Who Experienced At Least One Adverse Event (AE)	101 Participants

PRIMARY outcome

Timeframe: Up to approximately 17 months (through data cutoff date of 27-December-2017)

Population: The safety population consisted of all participants who received at least one dose of study treatment.

The number of all participants who discontinued study treatment due to an AE is presented.

Outcome measures

Measure	Pembrolizumab n=103 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Number of Participants Who Discontinued Study Treatment Due to an AE	4 Participants

PRIMARY outcome

Timeframe: Up to approximately 17 months (through data cutoff date of 27-December-2017)

Population: The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.

ORR was defined as the percentage of the participants in the analysis population who had a 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 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.

Outcome measures

Measure	Pembrolizumab n=102 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	16.7 Percentage of Participants Interval 10.0 to 25.3

SECONDARY outcome

Timeframe: Up to approximately 76 months

Population: The analysis population consisted of all participants who received at least one dose of study treatment.

OS was defined as the time from first day of study treatment to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months.

Outcome measures

Measure	Pembrolizumab n=103 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Survival (OS)	13.2 Months Interval 10.4 to 16.5

SECONDARY outcome

Timeframe: Up to approximately 76 months

Population: The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.

PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per RECIST 1.1 for participants is presented.

Outcome measures

Measure	Pembrolizumab n=102 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	2.8 Months Interval 2.7 to 3.5

SECONDARY outcome

Timeframe: Up to approximately 76 months

Population: The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.

DOR was defined as the time from first documented evidence of 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 until disease progression or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months.

Outcome measures

Measure	Pembrolizumab n=18 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	13.8 Months Interval 5.5 to NA indicates upper limit of 95% CI for DOR cannot be calculated at the time of last disease assessment due to insufficient number of participants with response

SECONDARY outcome

Timeframe: Up to approximately 76 months

Population: The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.

ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or a Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST assessed by blinded independent central review (BICR). The ORR per irRECIST for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.

Outcome measures

Measure	Pembrolizumab n=102 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)	18.6 Percentage of Participants Interval 11.6 to 27.6

SECONDARY outcome

Timeframe: Up to approximately 76 months

Population: The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.

PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRECIST based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per irRECIST for participants is presented.

Outcome measures

Measure	Pembrolizumab n=102 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)	2.8 Months Interval 2.7 to 4.0

SECONDARY outcome

Timeframe: Up to approximately 76 months

Population: The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.

DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST until disease progression or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months.

Outcome measures

Measure	Pembrolizumab n=19 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST)	13.8 Months Interval 5.4 to NA indicates upper limit of 95% CI for DOR cannot be calculated at the time of last disease assessment due to insufficient number of participants with response.

SECONDARY outcome

Timeframe: Day 21: Prior to the Cycle 2 (21-day cycle) Dose

Population: The analysis population consisted of participants who received 1 dose of study treatment, completed Cycle 1 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 2 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 2 is presented.

Outcome measures

Measure	Pembrolizumab n=30 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle)	8.70 μg/mL Standard Deviation 2.4

SECONDARY outcome

Timeframe: Day 63: Prior to the Cycle 4 (21-day cycle) Dose

Population: The analysis population consisted of participants who received 3 doses of study treatment, completed Cycle 3 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 4 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 4 is presented.

Outcome measures

Measure	Pembrolizumab n=26 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle)	16.2 μg/mL Standard Deviation 6.7

SECONDARY outcome

Timeframe: Day 105: Prior to the Cycle 6 (21-day cycle) Dose

Population: The analysis population consisted of participants who received 5 doses of study treatment, completed Cycle 5 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 6 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 6 is presented.

Outcome measures

Measure	Pembrolizumab n=17 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle)	22.9 μg/mL Standard Deviation 6.4

SECONDARY outcome

Timeframe: Day 147: Prior to the Cycle 8 (21-day cycle) Dose

Population: The analysis population consisted of participants who received 7 doses of study treatment, completed Cycle 7 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 8 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 8 is presented.

Outcome measures

Measure	Pembrolizumab n=13 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle)	26.9 μg/mL Standard Deviation 6.5

SECONDARY outcome

Timeframe: Day 231: Prior to the Cycle 12 (21-day cycle) Dose

Population: The analysis population consisted of participants who received 11 doses of study treatment, completed Cycle 11 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 12 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 12 is presented.

Outcome measures

Measure	Pembrolizumab n=8 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle)	33.8 μg/mL Standard Deviation 4.5

SECONDARY outcome

Timeframe: Day 315: Prior to the Cycle 16 (21-day cycle) Dose

Population: The analysis population consisted of participants who received 15 doses of study treatment, completed Cycle 15 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 16 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 16 is presented.

Outcome measures

Measure	Pembrolizumab n=4 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle)	34.6 μg/mL Standard Deviation 5.0

SECONDARY outcome

Timeframe: Day 0: 30 minutes after the end of infusion during Cycle 1 (21-day cycle)

Population: The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for Cmax analysis.

Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 1 (21-day cycle). The Cmax of pembrolizumab is presented.

Outcome measures

Measure	Pembrolizumab n=28 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle)	45.9 μg/mL Standard Deviation 10.9

SECONDARY outcome

Timeframe: Day 147: 30 minutes after the end of infusion during Cycle 8 (21-day cycle)

Population: The analysis population consisted of participants who received 8 doses of study treatment and had blood samples drawn for Cmax analysis.

Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 8 (21-day cycle). The Cmax of pembrolizumab is presented.

Outcome measures

Measure	Pembrolizumab n=12 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle)	68.7 μg/mL Standard Deviation 12.5

SECONDARY outcome

Timeframe: Day 2: 1 day after the end of infusion during Cycle 1 (21-day cycle)

Population: The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.

Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 1 day after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented.

Outcome measures

Measure	Pembrolizumab n=30 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Observed Serum Concentration of Pembrolizumab 1 Day After The End of Infusion During Cycle 1 (21-day Cycle)	34.0 μg/mL Standard Deviation 4.6

SECONDARY outcome

Timeframe: Day 6: 5 days after the end of infusion during Cycle 1 (21-day cycle)

Population: The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.

Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 5 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented.

Outcome measures

Measure	Pembrolizumab n=30 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Observed Serum Concentration of Pembrolizumab 5 Days After The End of Infusion During Cycle 1 (21-day Cycle)	18.4 μg/mL Standard Deviation 4.6

SECONDARY outcome

Timeframe: Day 15: 14 days after the end of infusion during Cycle 1 (21-day cycle)

Population: The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.

Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 14 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented.

Outcome measures

Measure	Pembrolizumab n=30 Participants Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Observed Serum Concentration of Pembrolizumab 14 Days After The End of Infusion During Cycle 1 (21-day Cycle)	11.9 μg/mL Standard Deviation 2.5

Adverse Events

Pembrolizumab

Serious events: 13 serious events

Other events: 98 other events

Deaths: 90 deaths

Pembrolizumab Second Course

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pembrolizumab n=103 participants at risk Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.	Pembrolizumab Second Course n=1 participants at risk Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.
Cardiac disorders Sinus tachycardia	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Hepatobiliary disorders Immune-mediated hepatitis	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Infections and infestations Bronchitis	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Infections and infestations Erysipelas	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Infections and infestations Pneumonia	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Injury, poisoning and procedural complications Rib fracture	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Decreased appetite	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Musculoskeletal and connective tissue disorders Arthritis	1.9% 2/103 • Number of events 2 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour rupture	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Nervous system disorders Cerebral haemorrhage	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Skin and subcutaneous tissue disorders Rash	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Vascular disorders Shock	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Vascular disorders Venous thrombosis limb	0.97% 1/103 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.

Other adverse events

Measure	Pembrolizumab n=103 participants at risk Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.	Pembrolizumab Second Course n=1 participants at risk Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.
Blood and lymphatic system disorders Anaemia	26.2% 27/103 • Number of events 32 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Endocrine disorders Hyperthyroidism	5.8% 6/103 • Number of events 6 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Endocrine disorders Hypothyroidism	26.2% 27/103 • Number of events 40 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Abdominal distension	6.8% 7/103 • Number of events 7 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Abdominal pain upper	6.8% 7/103 • Number of events 7 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Constipation	7.8% 8/103 • Number of events 9 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Diarrhoea	9.7% 10/103 • Number of events 12 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Nausea	6.8% 7/103 • Number of events 8 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Toothache	4.9% 5/103 • Number of events 5 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Gastrointestinal disorders Vomiting	10.7% 11/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
General disorders Asthenia	7.8% 8/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
General disorders Fatigue	15.5% 16/103 • Number of events 18 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
General disorders Pain	6.8% 7/103 • Number of events 8 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
General disorders Pyrexia	10.7% 11/103 • Number of events 14 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Infections and infestations Nasopharyngitis	5.8% 6/103 • Number of events 9 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Infections and infestations Upper respiratory tract infection	19.4% 20/103 • Number of events 25 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Alanine aminotransferase increased	27.2% 28/103 • Number of events 41 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Aspartate aminotransferase increased	18.4% 19/103 • Number of events 29 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Bilirubin conjugated increased	10.7% 11/103 • Number of events 26 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood alkaline phosphatase increased	8.7% 9/103 • Number of events 10 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood bilirubin increased	18.4% 19/103 • Number of events 36 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood bilirubin unconjugated increased	6.8% 7/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood cholesterol increased	7.8% 8/103 • Number of events 16 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood creatine phosphokinase increased	11.7% 12/103 • Number of events 22 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood glucose increased	6.8% 7/103 • Number of events 9 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood lactate dehydrogenase increased	16.5% 17/103 • Number of events 29 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood triglycerides increased	0.00% 0/103 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 3 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood urea increased	6.8% 7/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Blood uric acid increased	4.9% 5/103 • Number of events 14 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 2 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Gamma-glutamyltransferase increased	13.6% 14/103 • Number of events 17 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Neutrophil count decreased	10.7% 11/103 • Number of events 24 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Platelet count increased	5.8% 6/103 • Number of events 6 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Total bile acids increased	5.8% 6/103 • Number of events 13 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations Weight decreased	13.6% 14/103 • Number of events 14 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations White blood cell count decreased	12.6% 13/103 • Number of events 24 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations White blood cell count increased	9.7% 10/103 • Number of events 13 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Investigations White blood cells urine positive	6.8% 7/103 • Number of events 8 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Decreased appetite	18.4% 19/103 • Number of events 21 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Hypercholesterolaemia	6.8% 7/103 • Number of events 14 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Hyperglycaemia	11.7% 12/103 • Number of events 31 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Hypertriglyceridaemia	29.1% 30/103 • Number of events 67 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Hyperuricaemia	13.6% 14/103 • Number of events 23 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Hypoalbuminaemia	8.7% 9/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Metabolism and nutrition disorders Hyponatraemia	8.7% 9/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Musculoskeletal and connective tissue disorders Arthralgia	10.7% 11/103 • Number of events 13 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Musculoskeletal and connective tissue disorders Back pain	9.7% 10/103 • Number of events 10 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Musculoskeletal and connective tissue disorders Pain in extremity	7.8% 8/103 • Number of events 10 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	18.4% 19/103 • Number of events 25 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Nervous system disorders Dizziness	2.9% 3/103 • Number of events 3 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Nervous system disorders Headache	3.9% 4/103 • Number of events 4 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Psychiatric disorders Insomnia	8.7% 9/103 • Number of events 9 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Renal and urinary disorders Proteinuria	5.8% 6/103 • Number of events 6 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Respiratory, thoracic and mediastinal disorders Cough	9.7% 10/103 • Number of events 11 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.8% 6/103 • Number of events 6 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Skin and subcutaneous tissue disorders Pruritus	15.5% 16/103 • Number of events 24 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Skin and subcutaneous tissue disorders Rash	18.4% 19/103 • Number of events 20 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Skin and subcutaneous tissue disorders Vitiligo	14.6% 15/103 • Number of events 15 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	0.00% 0/1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.
Vascular disorders Hypertension	1.9% 2/103 • Number of events 2 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.	100.0% 1/1 • Number of events 1 • Up to approximately 76 months. The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

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