Trial Outcomes & Findings for Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)-China Extension (NCT NCT04934722)

NCT ID: NCT04934722

Last Updated: 2025-10-01

Results Overview

rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 186 participants
• Primary outcome timeframe: Up to approximately 17 months
• Results posted on: 2025-10-01

Participant Flow

A total of 186 Chinese participants were randomized and received treatment (global study [NCT04191096; n =7] and to the extension portion [n=179]). All safety results were reported on all participants treated.

Participant milestones

Measure	Pembrolizumab + Enzalutamide + ADT Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Overall Study STARTED	92	94
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	92	94

Reasons for withdrawal

Measure	Pembrolizumab + Enzalutamide + ADT Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Overall Study Death	4	3
Overall Study Participants Ongoing	88	91

Baseline Characteristics

Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)-China Extension

Baseline characteristics by cohort

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met	Total n=186 Participants Total of all reporting groups
Age, Continuous	68.5 Years STANDARD_DEVIATION 7.1 • n=5 Participants	67.4 Years STANDARD_DEVIATION 7.6 • n=7 Participants	67.9 Years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	94 Participants n=7 Participants	186 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	92 Participants n=5 Participants	94 Participants n=7 Participants	186 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	92 Participants n=5 Participants	94 Participants n=7 Participants	186 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	14.4 Months NA = lower limit and upper limit of 95% CI for rPFS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.	NA Months NA = Median, lower limit and upper limit of 95% CI for rPFS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.

PRIMARY outcome

Timeframe: Up to approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Overall Survival (OS)	NA Months Interval 14.4 to NA = Median and upper limit of 95% CI for OS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.	NA Months NA = Median, lower limit and upper limit of 95% CI for OS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to Approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response.

TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)	NA Months Interval 14.4 to NA = Median and upper limit of 95% CI for TFST cannot be calculated at the time of last disease assessment due to insufficient number of participants with events	NA Months NA = Median, lower limit and upper limit of 95% CI for TFST cannot be calculated at the time of last disease assessment due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to Approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response.

TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Time to First Symptomatic Skeletal-related Event (TTSSRE)	NA Months NA = Median, lower limit and upper limit of 95% CI for TTSSRE cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.	NA Months NA = Median, lower limit and upper limit of 95% CI for TTSSRE cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to Approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Time to Prostate-specific Antigen (PSA) Progression	NA Months NA = Median, lower limit and upper limit of 95% CI for Time to PSA Progression cannot be calculated at the time of last disease assessment due to insufficient number of participants with events	NA Months NA = Median, lower limit and upper limit of 95% CI for Time to PSA Progression cannot be calculated at the time of last disease assessment due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to Approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR	NA Months NA = Median, lower limit and upper limit of 95% CI for time to radiographic soft tissue progression cannot be calculated at the time of last disease assessment due to insufficient number of participants with events	NA Months NA = Median, lower limit and upper limit of 95% CI for time to radiographic soft tissue progression cannot be calculated at the time of last disease assessment due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to Approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion who received at least one dose of study treatment, and who had at least 1 BPI-SF assessment

TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a >2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids; a >2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score >4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=91 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=91 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use	NA Months Interval 9.4 to NA = Median and upper limit of 95% CI for TTPP cannot be calculated at the time of last disease assessment due to insufficient number of participants with events	NA Months NA = Median, lower limit and upper limit of 95% CI for TTPP cannot be calculated at the time of last disease assessment due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to Approximately 17 months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)	NA Months Interval 14.4 to NA = Median and upper limit of 95% CI for PFS2 cannot be calculated at the time of last disease assessment due to insufficient number of participants with events	NA Months NA = Median, lower limit and upper limit of 95% CI for PFS2 cannot be calculated at the time of last disease assessment due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to Approximately 17 Months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion who had a baseline PSA measurement and had data available for analysis

PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by >50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed >3 weeks from the original response.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=92 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Prostate-specific Antigen (PSA) Response Rate	93.5 Percentage of Participants Interval 86.3 to 97.6	98.9 Percentage of Participants Interval 94.2 to 100.0

SECONDARY outcome

Timeframe: Up to Approximately 17 Months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion with detectable PSA at baseline and had data available for analysis

PSA undetectable rate was defined as the percentage of participants with detectable PSA (> 0.2 ng/mL) at baseline, which becomes undetectable (< 0.2 ng/mL) during study treatment.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=90 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=93 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Prostate-specific Antigen (PSA) Undetectable	45.6 Percentage of Participants Interval 35.0 to 56.4	46.2 Percentage of Participants Interval 35.8 to 56.9

SECONDARY outcome

Timeframe: Up to Approximately 17 Months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion with measurable disease at baseline and had data available for analysis

ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on base scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=38 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=44 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR	73.7 Percentage of Participants Interval 56.9 to 86.6	65.9 Percentage of Participants Interval 50.1 to 79.5

SECONDARY outcome

Timeframe: Up to Approximately 17 Months

Population: All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion who demonstrated a CR or PR, and had data available for analysis

DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of a least 5 mm. PD per PCWG was the appearance of >2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for >6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data.

Outcome measures

Measure	Pembrolizumab + Enzalutamide + ADT n=38 Participants Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=44 Participants Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR	NA Months Interval 5.8 to NA = Median and 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	NA Months NA = Median, lower limit and 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 17 Months

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Approximately 17 Months

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm.

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab + Enzalutamide + ADT

Serious events: 24 serious events

Other events: 79 other events

Deaths: 4 deaths

Placebo + Enzalutamide + ADT

Serious events: 10 serious events

Other events: 79 other events

Deaths: 3 deaths

Serious adverse events

Measure	Pembrolizumab + Enzalutamide + ADT n=92 participants at risk Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 participants at risk Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Cardiac disorders Acute myocardial infarction	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Cardiac disorders Arteriosclerosis coronary artery	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Cardiac disorders Autoimmune myocarditis	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Cardiac disorders Myocardial infarction	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Endocrine disorders Adrenal insufficiency	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Endocrine disorders Hypophysitis	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Endocrine disorders Immune-mediated thyroiditis	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Anal incontinence	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Gastrointestinal ulcer perforation	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Upper gastrointestinal perforation	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
General disorders Pyrexia	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Hepatobiliary disorders Cholecystitis	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Hepatobiliary disorders Cholelithiasis	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Hepatobiliary disorders Hepatic function abnormal	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Hepatobiliary disorders Immune-mediated hepatitis	3.3% 3/92 • Number of events 3 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Infections and infestations Septic shock	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Infections and infestations Upper respiratory tract infection	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Infections and infestations Urinary tract infection	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Injury, poisoning and procedural complications Brain contusion	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Injury, poisoning and procedural complications Thoracic vertebral fracture	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Alanine aminotransferase increased	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Neutrophil count decreased	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Platelet count decreased	3.3% 3/92 • Number of events 3 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Nervous system disorders Cerebral infarction	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Nervous system disorders Dizziness	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Psychiatric disorders Insomnia	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Renal and urinary disorders Immune-mediated nephritis	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Renal and urinary disorders Urinary incontinence	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Respiratory, thoracic and mediastinal disorders Immune-mediated lung disease	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Skin and subcutaneous tissue disorders Immune-mediated dermatitis	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Vascular disorders Aortic dissection	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Vascular disorders Thrombosis	0.00% 0/92 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Vascular disorders Venous thrombosis limb	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.

Other adverse events

Measure	Pembrolizumab + Enzalutamide + ADT n=92 participants at risk Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	Placebo + Enzalutamide + ADT n=94 participants at risk Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
Blood and lymphatic system disorders Anaemia	27.2% 25/92 • Number of events 34 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	14.9% 14/94 • Number of events 19 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Endocrine disorders Hypothyroidism	9.8% 9/92 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	4.3% 4/94 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Constipation	7.6% 7/92 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	6.4% 6/94 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Diarrhoea	8.7% 8/92 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	7.4% 7/94 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Nausea	4.3% 4/92 • Number of events 4 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	7.4% 7/94 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Gastrointestinal disorders Toothache	3.3% 3/92 • Number of events 4 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	6.4% 6/94 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
General disorders Fatigue	9.8% 9/92 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	7.4% 7/94 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
General disorders Malaise	10.9% 10/92 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	4.3% 4/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
General disorders Pyrexia	8.7% 8/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	2.1% 2/94 • Number of events 2 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Hepatobiliary disorders Hepatic function abnormal	1.1% 1/92 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Infections and infestations Upper respiratory tract infection	5.4% 5/92 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	8.5% 8/94 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Alanine aminotransferase increased	19.6% 18/92 • Number of events 20 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	22.3% 21/94 • Number of events 22 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Aspartate aminotransferase increased	15.2% 14/92 • Number of events 16 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	18.1% 17/94 • Number of events 17 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Blood alkaline phosphatase increased	5.4% 5/92 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Blood bilirubin increased	4.3% 4/92 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Blood cholesterol increased	6.5% 6/92 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	2.1% 2/94 • Number of events 2 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Blood thyroid stimulating hormone increased	5.4% 5/92 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	8.5% 8/94 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Lymphocyte count decreased	2.2% 2/92 • Number of events 2 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Neutrophil count decreased	5.4% 5/92 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Platelet count decreased	10.9% 10/92 • Number of events 19 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	10.6% 10/94 • Number of events 17 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Weight decreased	4.3% 4/92 • Number of events 4 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations Weight increased	8.7% 8/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	12.8% 12/94 • Number of events 15 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Investigations White blood cell count decreased	7.6% 7/92 • Number of events 12 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Decreased appetite	12.0% 11/92 • Number of events 11 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hypercholesterolaemia	5.4% 5/92 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	4.3% 4/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hyperglycaemia	17.4% 16/92 • Number of events 26 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	21.3% 20/94 • Number of events 33 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hyperkalaemia	4.3% 4/92 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	6.4% 6/94 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hyperlipidaemia	8.7% 8/92 • Number of events 13 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	7.4% 7/94 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hypertriglyceridaemia	6.5% 6/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	4.3% 4/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hyperuricaemia	5.4% 5/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	6.4% 6/94 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hypocalcaemia	7.6% 7/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	6.4% 6/94 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hypokalaemia	4.3% 4/92 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	6.4% 6/94 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Metabolism and nutrition disorders Hyponatraemia	7.6% 7/92 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	3.2% 3/94 • Number of events 3 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Musculoskeletal and connective tissue disorders Arthralgia	8.7% 8/92 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	11.7% 11/94 • Number of events 15 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Musculoskeletal and connective tissue disorders Back pain	2.2% 2/92 • Number of events 2 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	9.6% 9/94 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Musculoskeletal and connective tissue disorders Pain in extremity	8.7% 8/92 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	8.5% 8/94 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Nervous system disorders Dizziness	9.8% 9/92 • Number of events 11 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	7.4% 7/94 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Nervous system disorders Headache	5.4% 5/92 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	1.1% 1/94 • Number of events 1 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Renal and urinary disorders Pollakiuria	5.4% 5/92 • Number of events 7 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	5.3% 5/94 • Number of events 5 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Respiratory, thoracic and mediastinal disorders Cough	5.4% 5/92 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	3.2% 3/94 • Number of events 3 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Skin and subcutaneous tissue disorders Immune-mediated dermatitis	7.6% 7/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	0.00% 0/94 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Skin and subcutaneous tissue disorders Pruritus	6.5% 6/92 • Number of events 6 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	4.3% 4/94 • Number of events 4 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Skin and subcutaneous tissue disorders Rash	25.0% 23/92 • Number of events 29 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	9.6% 9/94 • Number of events 10 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Vascular disorders Hot flush	8.7% 8/92 • Number of events 8 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	9.6% 9/94 • Number of events 9 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
Vascular disorders Hypertension	15.2% 14/92 • Number of events 16 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.	11.7% 11/94 • Number of events 15 • Up to approximately 17 months All-cause mortality was reported on all randomized participants and adverse events (serious and non-serious) were reported on all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.

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 will comply with the requirements for publication of study results. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
• Publication restrictions are in place

Restriction type: OTHER