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

Merck Sharp & Dohme LLC

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.

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)…

Eligibility

Age range: 18+ years
Sex: Male
Healthy volunteers: No

Detailed criteria

Inclusion Criteria: * For Cohorts A, B, C, D, E, G, J: Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology * For Cohorts F, H, I: Has t-NE or de novo metastatic prostate cancer defined by ≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment. Epstein criteria of neuroendocrine differentiation in prostate cancer is used for eligibility. Specimens must have one of the morphologies o…

Interventions

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

Locations (21)

Call for Information (Investigational Site 2041)
Aurora, Colorado
Call for Information (Investigational Site 2091)
Cleveland, Ohio
Call for Information (Investigational Site 2094)
Portland, Oregon
Call for Information (Investigational Site 0008)
Pittsburgh, Pennsylvania
Call for Information (Investigational Site 0019)
Myrtle Beach, South Carolina
Call for Information (Investigational Site 2090)
Germantown, Tennessee