Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)

Summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration resistant prostate cancer (mCRPC). There will be ten cohorts in this study: Cohort A will receive pembrolizumab + olaparib, Cohort B will receive pembrolizumab + docetaxel + prednisone, Cohort C will receive pembrolizumab + enzalutamide, Cohort D will receive pembrolizumab + abiraterone + prednisone Cohort E will receive pembrolizumab+lenvatinib, Cohort F will receive pembrolizumab+lenvatinib, Cohort G will receive pembrolizumab/vibostolimab coformulation (MK-7684A), Cohort H will receive pembrolizumab/vibostolimab coformulation, Cohort I will receive pembrolizumab+carboplatin+etoposide in Arm 1 and carboplatin+etoposide in Arm 2 and Cohort J will receive belzutifan in Arm1 and Pembrolizumab+belzutifan in Arm 2. Outcome measures will be assessed individually for each cohort.

Timeline

Start

2016-11-17

Primary completion

2027-10-22

Completion

2028-07-24

Publications

• Results Yu EY, Ferrario C, Linch MD, Stoeckle M, Laguerre B, Arranz JA, Todenhofer T, Fong PC, Piulats JM, Berry W, Emmenegger U, Mourey L, Joshua AM, Mar N, Appleman LJ, Conter HJ, Gravis G, Li XT, Schloss C, Poehlein C, de Bono JS. Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D. Eur Urol Oncol. 2025 Jun;8(3):641-651. doi: 10.1016/j.euo.2024.05.013. Epub 2024 Jun 25.
• Results Yu EY, Berry WR, Gurney H, Retz M, Conter HJ, Laguerre B, Fong PCC, Ferrario C, Todenhofer T, Gravis G, Piulats JM, Emmenegger U, Shore ND, Romano E, Mourey L, Li XT, Poehlein CH, Schloss C, Appleman LJ, de Bono JS. Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study. Eur Urol Oncol. 2024 Jun;7(3):509-518. doi: 10.1016/j.euo.2023.10.008. Epub 2023 Nov 7.
• Augustin M, Laguerre B, Baldini C, Zedan AH, Gonzalez-Billalabeitia E, Fong PC, Zukov R, Hammerer P, Prentice M, Shore N, Necchi A, Todenhofer T, Kessler ER, Kose F, Gurney H, Valderrama BP, Zhu P, Imai K, Liu Y, McDermott R. Pembrolizumab Plus Lenvatinib in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort E. Eur Urol Oncol. 2026 May 2:S2588-9311(26)00084-2. doi: 10.1016/j.euo.2026.03.026. Online ahead of print.
• Fong PC, Kwiatkowski M, Mosca A, Valderrama BP, Li C, Huang YH, Zedan AH, Kuc K, Wiechno P, Laguerre B, Gonzalez-Billalabeitia E, Osipov M, Sener Dede D, Goh JC, Daugaard G, Zhu P, Imai K, Liu Y, Arranz Arija JA. Vibostolimab Coformulated with Pembrolizumab in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: KEYNOTE-365 Cohort G. Eur Urol Focus. 2026 Mar;12(2):168-173. doi: 10.1016/j.euf.2025.07.018. Epub 2025 Aug 11.
• Yu EY, Kolinsky MP, Berry WR, Retz M, Mourey L, Piulats JM, Appleman LJ, Romano E, Gravis G, Gurney H, Bogemann M, Emmenegger U, Joshua AM, Linch M, Sridhar S, Conter HJ, Laguerre B, Massard C, Li XT, Schloss C, Poehlein CH, de Bono JS. Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study. Eur Urol. 2022 Jul;82(1):22-30. doi: 10.1016/j.eururo.2022.02.023. Epub 2022 Apr 6.

Drugs

Indications