ASCO 2017: Phase 1b/2 keynote-365 trial: Pembrolizumab (pembro) combination therapy in metastatic castration-resistant prostate cancer

Chicaco, IL (UroToday.com) Dr. Evan Yu and colleagues presented their trial design for KEYNOTE-365, a phase Ib/II trial assessing pembrolizumab combination therapy for metastatic castration-resistant prostate cancer (mCRPC) at the prostate cancer sessions at the 2017 ASCO annual meeting. We know that approved treatments for mCRPC (eg, enzalutamide and docetaxel) may increase programmed death ligand 1 (PD-L1) expression and facilitate neoantigen release. Furthermore, olaparib, a PARP inhibitor, has shown activity in mCRPC with DNA-repair defects. The objective of this study is to evaluate the safety and efficacy of pembrolizumab with olaparib (cohort A), docetaxel + prednisone (cohort B), or enzalutamide (cohort C) in mCRPC patients.

The cohort allocation for this study relies on prior treatment received. Patients in cohort A require prior docetaxel (treatment with 1 other chemotherapy and ≤2 second-generation hormonal manipulations allowable), cohort B requires prior abiraterone acetate or enzalutamide (but not both), and cohort C requires prior abiraterone acetate. Additional eligibility criteria include (i) confirmed prostate adenocarcinoma, (ii) disease progression ≤6 months before screening, (iii) ongoing androgen deprivation with castrate level testosterone, and (iv) provision of non-irradiated tumor sample. Pembrolizumab 200 mg will be given every 3 weeks with either olaparib 400 mg twice daily (cohort A), docetaxel 75 mg/m2 every 3 weeks + prednisone 5 mg twice daily (cohort B), or enzalutamide 160 mg once daily (cohort C). Pembrolizumab treatment will continue for up to 35 cycles or until disease progression or unacceptable adverse events, and patients in cohort B may receive a maximum of 10 cycles of docetaxel + prednisone. Response to combination therapy will be evaluated by PSA levels every 3 weeks and by imaging every 9 weeks for the first year and every 12 weeks thereafter.

Primary end points are safety and PSA response rate (decline of ≥50% from baseline twice ≥3 weeks apart), and secondary end points will be (i) time to PSA progression, (ii) progression-free survival, (iii) overall survival, and (iv) overall response rate. The trial is currently enrolling in the US, Canada, Europe, Australia and New Zealand, and will continue enrolling until 70 patients are enrolled for each cohort.
Clinical trial: NCT02861573

Presented By: Evan Y. Yu, MD, Seattle Cancer Care Alliance, Seattle, WA, USA

Co-Authors: Haiyan Wu, Charles Schloss

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
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