Trial Outcomes & Findings for Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)-China Extension (NCT NCT04907227)

Last Updated: 2024-07-12

Results Overview

OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit Kaplan-Meier (K-M) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

81 participants

Primary outcome timeframe

Up to 19.8 months

Results posted on

2024-07-12

Participant Flow

Protocol-specified final analysis for all primary and secondary outcome measures was performed with the primary completion data cutoff. Twenty-one participants in the China extension study were also included in the global study for MK-3475-921 (NCT03834506).

Participant milestones

Participant milestones
Measure	Pembrolizumab + Docetaxel Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Overall Study STARTED	41	40
Overall Study Treated	41	40
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	41	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab + Docetaxel Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Overall Study Death	12	8
Overall Study Withdrawal by Subject	2	2
Overall Study Withdrawal By Parent/Guardian	1	0
Overall Study Sponsor Decision	25	30
Overall Study Physician Decision	1	0

Baseline Characteristics

Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)-China Extension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Total n=81 Participants Total of all reporting groups
Age, Continuous	67.1 Years STANDARD_DEVIATION 7.5 • n=5 Participants	68.0 Years STANDARD_DEVIATION 7.5 • n=7 Participants	67.6 Years STANDARD_DEVIATION 7.5 • 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	41 Participants n=5 Participants	40 Participants n=7 Participants	81 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	40 Participants n=5 Participants	39 Participants n=7 Participants	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 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	41 Participants n=5 Participants	40 Participants n=7 Participants	81 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 19.8 months

Population: All randomized participants in the intent to treat population who had data available for analysis

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Overall Survival (OS)	16.3 Months Interval 10.6 to NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.	13.9 Months Interval 11.1 to NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.

PRIMARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population who had data available for analysis

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. Radiological progression as per 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 K-M method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
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)	6.4 Months Interval 4.2 to NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.	11.2 Months Interval 6.3 to NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population who had data available for analysis

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 K-M method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)	9.3 Months Interval 5.8 to 10.1	8.3 Months Interval 4.9 to 10.2

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population, who had a PSA measurement at baseline, and had data available for analysis

The Prostate-specific Antigen (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. The analysis was performed on participants who had baseline PSA measurements. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Prostate-specific Antigen (PSA) Response Rate	24.4 Percentage of participants Interval 12.4 to 40.3	22.5 Percentage of participants Interval 10.8 to 38.5

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population, 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 bone 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). Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=17 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=15 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Objective Response Rate (ORR) 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)	17.6 Percentage of participants Interval 3.8 to 43.4	13.3 Percentage of participants Interval 1.7 to 40.5

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population, who demonstrated a CR or PR, and had data available for analysis

DOR was the time from first evidence of complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease \[NED\] on bone scan per PCWG) or partial response (PR: ≥30% decrease in the sum of diameters of target lesions per RECIST 1.1; non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG) until progressive disease (PD) or death. PD per RECIST 1.1 was ≥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 ≥5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan that were confirmed to not represent tumor flare and persisted for ≥6 weeks. DOR was calculated using the product-limit K-M method. Participants who did not progress were censored at last disease assessment. Per protocol final analysis for this outcome measure was done with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=3 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=2 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Duration of Response (DOR) 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)	NA Months NA = Median, upper limit, and lower limit not reached at time of data cut-off due to insufficient number of responding participants with relapse.	NA Months NA = Median, upper limit, and lower limit not reached at time of data cut-off due to insufficient number of responding participants with relapse.

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All participants in the participant-reported outcomes (PRO) full analysis set who received ≥1 dose of study treatment and who had ≥1 PRO assessment available

TTPP was time from randomization to pain progression (PP) per BPI-SF Item 3 and AQA score. BPI-SF assesses pain intensity; for item 3, responses to "Please rate your pain at its worst in the last 24 hours" are scored from 0 (no pain) to 10 (worst pain). A higher score indicates greater pain. AQA captures the intensity of analgesic use, scored from 0 (no use) to 7 (strong opioid use). A higher score indicates higher intensity of use. For participants asymptomatic at baseline, PP was ≥2-point change from baseline in Item 3 score OR opioid use initiation. For those symptomatic at baseline, PP was ≥2-point change from baseline in Item 3 score, a score of ≥4, no decrease in average opioid use OR any increase in opioid use (e.g. 1 point change in AQA score). TTPP was assessed by product-limit K-M method. Participants with \>2 consecutive unevaluable visits were censored at last assessment. Per protocol final analysis for this outcome measure was done with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score	NA Months NA = Median, upper limit, and lower limit not reached at time of data cut-off due to insufficient number of participants with an event.	NA Months NA = Median, upper limit, and lower limit not reached at time of data cut-off due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population who had data available for analysis

SSRE was the time from randomization to the first symptomatic skeletal-related event defined as: 1. use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. occurrence of spinal cord compression 4. tumor-related orthopedic surgical intervention, whichever occurs first. The SSRE was calculated using the product-limit K-M method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Time to First Symptomatic Skeletal-related Event (SSRE)	NA Months NA = Median, upper limit, and lower limit not reached at time of data cut-off due to insufficient number of participants with an event.	NA Months Interval 10.0 to NA = Median and upper limit not reached at time of data cut-off due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population, who had a PSA measurement at baseline, and had data available for analysis

The 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 was PSA decline from baseline; OR 2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline. Time to PSA progression was calculated using the product-limit K-M method for censored data. Participants without PSA progression were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Time to Prostate-specific Antigen (PSA) Progression	5.0 Months Interval 3.0 to 9.6	3.7 Months Interval 2.8 to 6.7

SECONDARY outcome

Timeframe: Up to 19.8 months

Population: All randomized participants in the intent to treat population who had data available for analysis

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 K-M method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of 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)	NA Months Interval 8.2 to NA = Median and upper limit not reached at time of data cut-off due to insufficient number of participants with an event.	11.2 Months Interval 8.2 to NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to 17 months

Population: All participants who received ≥1 dose of study treatment

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 could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, final analysis for this outcome measure was performed with the primary completion data cutoff. The number of participants who experienced an AE is presented.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Number of Participants Who Experienced an Adverse Event (AE)	37 Participants	34 Participants

SECONDARY outcome

Timeframe: Up to 14 months

Population: All participants who received ≥1 dose of study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab + Docetaxel n=41 Participants Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 Participants Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)	3 Participants	6 Participants

Adverse Events

Pembrolizumab + Docetaxel

Serious events: 11 serious events

Other events: 36 other events

Deaths: 12 deaths

Placebo + Docetaxel

Serious events: 12 serious events

Other events: 34 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Serious adverse events
Measure	Pembrolizumab + Docetaxel n=41 participants at risk Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.	Placebo + Docetaxel n=40 participants at risk Participants received placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly received dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
Blood and lymphatic system disorders Anaemia	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Myelosuppression	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Neutropenia	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Cardiac failure	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Death	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Multiple organ dysfunction syndrome	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations COVID-19	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Endophthalmitis	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Gastrointestinal infection	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pneumonia	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Sepsis	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Radiation proctitis	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood creatinine increased	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Neutrophil count decreased	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Platelet count decreased	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations White blood cell count decreased	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Decreased appetite	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Diabetes mellitus	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Cerebral haemorrhage	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Spinal cord compression	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Acute kidney injury	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Calculus bladder	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Haematuria	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.0% 2/40 • Number of events 3 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.4% 1/41 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/40 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Vascular disorders Embolism	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Vascular disorders Venous thrombosis limb	0.00% 0/41 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 1/40 • Number of events 1 • Up to approximately 31 months All-cause mortality: All randomized participants; AEs: all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.