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)

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.

Timeline

Start

2019-07-28

Primary completion

2022-12-12

Completion

2026-06-08

Publications

• Results Graff JN, Burotto M, Fong PC, Pook DW, Zurawski B, Manneh Kopp R, Salinas J, Bylow KA, Kramer G, Ratta R, Kwiatkowski M, Retz M, Kwak C, Arranz Arija JA, Gurney H, Matsubara N, Villanueva L, Todenhofer T, Liang LW, Todoric J, Imai K, Stenzl A; KEYNOTE-641 Investigators. Pembrolizumab plus enzalutamide versus placebo plus enzalutamide for chemotherapy-naive metastatic castration-resistant prostate cancer: the randomized, double-blind, phase III KEYNOTE-641 study. Ann Oncol. 2025 Aug;36(8):976-987. doi: 10.1016/j.annonc.2025.05.007. Epub 2025 May 16.
• Graff JN, Liang LW, Kim J, Stenzl A. KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. Future Oncol. 2021 Aug;17(23):3017-3026. doi: 10.2217/fon-2020-1008. Epub 2021 May 28.

Drugs

Indications