PD-1 inhibition has demonstrated improved survival for patients with various solid tumors, but its role in prostate cancer has yet to be defined. Based on observations that PD-L1 expression is increased upon resistance to enzalutamide and androgen inhibition modulates the immune response to prostate cancer, we hypothesized that the addition of the PD-1 inhibitor pembrolizumab to enzalutamide at resistance could result in clinically important anti-tumor activity.
We treated men with mCRPC progressing on the androgen receptor antagonist enzalutamide on a phase II study of pembrolizumab 200 mg IV every 3 weeks for 4 doses with continued enzalutamide. Prior chemotherapy for mCRPC was prohibited. The primary endpoint is the proportion of men with a prostate specific antigen (PSA) response ≥ 50%. The secondary endpoints are objective disease response, PSA progression free survival, and overall survival. The sample size sufficient to detect a 25% response rate served as the basis for the statistical design. Tissue biopsy is performed if feasible.
As of 22 July 2016, 20 patients have completed pembrolizumab treatment with a median follow up of 18 weeks. 4 of 20 subjects treated to date (20%) have achieved a confirmed PSA reduction ≥ 50%, reached a serum PSA
Early results demonstrate reproducible, profound, and - to date - durable responses to PD-1 inhibition with enzalutamide in men with mCRPC.
Clinical trial identification
Legal entity responsible for the study
Oregon Health & Science University
Merck Sharp & Dohme Corporation
J.N. Graff: I have received research funding from Merck to perform this research. I have received honoraria from Astellas. C.G. Drake: Received research funding from Bristol Myers Squibb (BMS). He has received consulting fees from BMS, Merck, Astra Zeneca (AZ) and Medimmune. He has patents licensed from AZ and Medimmune. W.L. Redmond: Received research grants, consulting fees, and/or royalties from Bristol-Myers Squibb, Merck, Galectin Therapeutics, and Nektar Therapeutics.
T.M. Beer: Research funding from Astellas and Medivation; consulting fees from Astellas.
All other authors have declared no conflicts of interest.