The clinical trial KEYNOTE-365 (NCT02861573) is a nonrandomized, multi-cohort, open-label phase 1b/2 study designed to evaluate the safety and tolerability of Pembrolizumab and Olaparib in group A compared to the combination of docetaxel + prednisone in group B and enzalutamide in group C, specifically in patients with mCRPC. This is an ongoing study with active enrollment at 42 sites in USA, Canada, Europe, Australia and New-Zealand. The investigators plan to enroll approximately 210 pts (70 per cohort).
Eligible patients include those with histologically or cytologically confirmed prostate cancer without small-cell histology who have progressed within 6 months before screening and have undergone androgen deprivation therapy with castrated serum testosterone levels (<50 ng/dL). Cohort assignment is dependent on previous mCRPC treatments with patients previously treated with docetaxel (1 other chemotherapy and ≤2 second-generation hormonal manipulations are allowed) included in group A; patients previously treated with abiraterone acetate or enzalutamide (but not both) included in group B; and patients previously treated with abiraterone acetate included in cohort C. Patients must provide a tumor sample from a non-irradiated site for biomarker analyses.
Exclusion criteria include immunodeficiency status or receipt of immunosuppressive therapy within 7 days before treatment allocation, known active CNS metastasis, prior Radium therapy, and history of pneumonitis or current pneumonitis.
In group A - Pembrolizumab 200 mg will be administered every 3 weeks in combination with Olaparib 400 mg twice daily. Patients who discontinue Pembrolizumab after 2 years may be eligible for up to an additional year of treatment upon radiographic progression. In group B - docetaxel 75 mg/m2 will be given every 3 weeks + prednisone 5 mg twice daily for a maximum of 10 cycles. In Group C - enzalutamide 160 mg will be given daily. Patients who discontinue 1 drug in a combination because of a drug-related adverse event will be allowed to continue the other drug.
Response will be assessed with PSA levels every 3 weeks and with radiologic imaging every 9 weeks for the first year and every 12 weeks thereafter. Adverse events will be monitored throughout the trial and for 30 days after treatment end, and graded according to NCI CTCAE v4.0.
The primary efficacy end point is PSA response rate (decline of ≥50% from baseline measured twice at least 3 weeks apart). Secondary end points include time to PSA progression, overall survival, and radiographic progression-free survival, objective response rate, and duration of response.
Presented by: Yu E.Y., Wu H., Schloss C.
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto
at the #EAU17 -March 24-28, 2017- London, England