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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)

NCT04191096 · Status: COMPLETED · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 1251

Last updated 2026-04-29

Study results available
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Summary

This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus Androgen Deprivation Therapy (ADT) versus placebo plus enzalutamide plus ADT in participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS). As of 19-JAN-2023, the study was unblinded and all study participants stopped ongoing treatment with pembrolizumab/placebo and will continue to receive Standard of Care treatment until meeting protocol-specified discontinuation criteria if deriving clinical benefit. Safety analysis will be performed at the end of the study; there will be no further analyses for efficacy and electronic patient-reported outcome (ePRO) endpoints collected from participants beyond the IA1 cutoff date. All study participants will stop ongoing treatment with pembrolizumab/placebo. Exceptions may be requested for study participants who, in the assessment of their study physician, are benefitting from the combination of enzalutamide and pembrolizumab, after consulting with the Sponsor. All other study participants should be discontinued from study and be offered standard of care (SOC) treatment as deemed necessary by the Investigator. If enzalutamide as SOC is not accessible off study to the participant, central sourcing may continue. As of Amendment 04, disease progression will no longer be centrally verified, participants will only be assessed locally. As of Amendment 4, Second Course treatment is not an option for participants. There are currently no participants in the Second Course Phase.

Conditions

Interventions

BIOLOGICAL

Pembrolizumab

Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.

DRUG

Enzalutamide

Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.

DRUG

Androgen Deprivation Therapy (ADT)

Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.

OTHER

Placebo

Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles.

Sponsors & Collaborators

Principal Investigators

  • Medical Director · Merck Sharp & Dohme LLC

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
MALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-02-12
Primary Completion
2022-10-31
Completion
2026-04-08
FDA Drug
Yes

Countries

  • United States
  • Australia
  • Austria
  • Brazil
  • Canada
  • Chile
  • China
  • Colombia
  • Denmark
  • Finland
  • France
  • Germany
  • Ireland
  • Israel
  • Italy
  • Japan
  • Mexico
  • Netherlands
  • New Zealand
  • Peru
  • Poland
  • Russia
  • South Korea
  • Spain
  • Switzerland
  • Taiwan
  • Thailand
  • Turkey (Türkiye)
  • United Kingdom

Study Locations

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Entities

Drugs
Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04191096 on ClinicalTrials.gov