NCT02861573

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

Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 1,200 (estimated)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Assignment of patients to a cohort will be based on prior treatment as outlined in the eligibility criteria. Participants who discontinue pembrolizumab or vibostolimab+pembrolizumab after 35 infusions for reasons other than disease progression or intolerability, or who discontinue pembrolizumab or coformulation of pembrolizumab/vibostolimab after attaining a complete response (and had at least 8 administrations of pembrolizumab or pembrolizumab/vibostolimab coformulation and at least 2 treatments with pembrolizumab or pembrolizumab/vibostolimab coformulation beyond initial complete response) may be eligible to receive a second course of treatment that includes up to 17 additional infusions (approximately 1 year) of pembrolizumab monotherapy or pembrolizumab/vibostolimab coformulation after they have experienced radiographic disease progression after stopping first course treatment. Effective with Protocol Amendment 08, enrollment into Cohorts A, B, C, and D was closed. Effective with Protocol Amendment 14, enrollment into Cohorts E, F, G, and H was closed (not due to any safety issues). No further efficacy and survival follow-up assessments will be collected in Cohorts A through H. Effective with Protocol Amendment 16, enrollment into Cohort J was closed (not due to any safety issues).

Conditions

• Metastatic Castration-Resistant Prostate Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab 200 mg	IV Q3W
DRUG	Olaparib 400 mg	Eight 50-mg capsules PO BID
DRUG	Docetaxel 75 mg/m^2	IV Q3W
DRUG	Prednisone 5 mg	One 5-mg tablet PO BID
DRUG	Enzalutamide 160 mg	Four 40-mg capsules, four 40-mg tablets, or two 80-mg tablets PO QD
OTHER	Dexamethasone 8 mg	Premedication for Cohort B given PO at 12, 3, and 1 hours prior to docetaxel infusion Q3W
DRUG	Olaparib 300 mg	Two 150-mg tablets PO BID
DRUG	Abiraterone acetate 1000 mg	Two 500-mg or four 250-mg tablets PO QD
DRUG	Lenvatinib	20 mg PO QD
BIOLOGICAL	Pembrolizumab/Vibostolimab coformulation	IV Q3W
DRUG	Carboplatin	IV Q3W
DRUG	Etoposide	IV on Days 1, 2 and 3 of each cycle
BIOLOGICAL	Belzutifan 120mg	PO QD

Timeline

• Start date: 2016-11-17
• Primary completion: 2027-10-22
• Completion: 2028-07-24
• First posted: 2016-08-10
• Last updated: 2026-02-17

Locations

21 sites across 15 countries: United States, Australia, Canada, Denmark, France, Ireland, Italy, Mexico, Netherlands, New Zealand, Poland, Spain, Sweden, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study