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Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641) | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE3

Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-641)

NCT03834493•Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

Summary

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and enzalutamide in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC, are abiraterone-naïve, or are intolerant to or progressed on abiraterone acetate. There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to 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.

Eligibility

Age

18 - No limit years

Sex

MALE

Healthy Volunteers

Inclusion Criteria

•Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
•Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to randomization
•Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
•Has met one of the following criteria with regard to abiraterone acetate exposure: (1) is abiraterone-naïve; (2) received prior abiraterone acetate for the treatment of mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3) received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with bone progression)
•Has ongoing androgen deprivation with serum testosterone \<50 ng/dL (\<2.0 nM)
•Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
•Participants must agree to the following during the study treatment period and for at least 90 days after the last dose of enzalutamide: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom
•Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
•Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization

Exclusion Criteria

•Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
•Has an active autoimmune disease that has required systemic treatment in past 2 years
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
•Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
•Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
•Has an active infection (including tuberculosis) requiring systemic therapy
•Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
•Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B virus (HBV) or known active hepatitis C virus (HCV) infection
•Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
•Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
+16 more criteria

Locations (259)

University of South Alabama, Mitchell Cancer Institute ( Site 0065)

Mobile, Alabama, United States

Providence Medical Foundation-Oncology ( Site 0069)

Fullerton, California, United States

UCLA Hematology/Oncology - Santa Monica ( Site 0081)

Los Angeles, California, United States

University of Colorado Cancer Center ( Site 0022)

Aurora, Colorado, United States

Smilow Cancer Hospital at Yale New Haven ( Site 0038)

New Haven, Connecticut, United States

Moffitt Cancer Center ( Site 0080)

Tampa, Florida, United States

Georgia Cancer Center at Augusta University ( Site 0026)

Augusta, Georgia, United States

Mount Sinai Hospital ( Site 0042)

Chicago, Illinois, United States

Methodist Hospitals. ( Site 0008)

Merrillville, Indiana, United States

Tulane Cancer Center ( Site 0066)

New Orleans, Louisiana, United States

Key Dates

Start Date

July 28, 2019

Primary Completion Date

December 12, 2022

Completion Date

May 29, 2026

Last Updated

July 18, 2025

Enrollment

1,244

ACTUAL participants

Conditions

Prostatic Neoplasms

Interventions

Pembrolizumab

BIOLOGICAL

Enzalutamide

DRUG

Placebo

DRUG

A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer

NCT07225946

Prostatic Neoplasms, Castration-Resistant

View study

RECRUITINGPHASE1/PHASE2

64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE)

NCT04868604

Prostatic Neoplasms, Castration-Resistant

View study

RECRUITING

Prostate Active Surveillance Study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 18, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)

Inclusion Criteria

Exclusion Criteria

A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer

64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE)

Prostate Active Surveillance Study

Study of TVB-2640 in Men With Metastatic Castration-Resistant Prostate Cancer

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