Three Keytruda Combinations Show Signs of Efficacy in Metastatic CRPC

Three Keytruda Combinations Show Signs of Efficacy in Metastatic CRPC
Combining the immune checkpoint inhibitor Keytruda (pembrolizumab) with either a PARP inhibitor, chemotherapy, or hormone therapy led to promising signs of activity in metastatic castration-resistant prostate cancer (mCRPC) patients in a Phase 1b/2 trial, Merck — Keytruda's developer — announced. The findings were presented at the 2019 Genitourinary Cancers Symposium (ASCO GU), Feb. 14-16 in San Francisco, California. Keytruda, by Merck (MSD outside the U.S. and Canada), binds to the PD-1 receptor on immune cells and prevents the binding of the PD-L1 ligand produced by cancer cells. Cancer cells use this mechanism to evade immune surveillance, and thus, Keytruda is meant to restore a functional immune system that effectively fights cancer. The KEYNOTE-365 Phase 1b/2 trial (NCT02861573) — still looking for participants — was designed to test multiple Keytruda combinations for the treatment of men with metastatic castration-resistant prostate cancer. The trial has four arms, or cohorts, receiving Keytruda in combination with another therapy: Cohort A: The PARP inhibitor Lynparza (olaparib); Cohort B: The chemotherapy docetaxel and prednisone; Cohort C: The hormone therapy Xtandi (enzalutamide); Cohort D: Zytiga (abiraterone acetate) and prednisone. It is designed to determine the combinations' safety, overall response rates, and PSA response rate (deemed as a 50% or greater reduction in PSA levels) as primary measures. Secondary endpoints include disease control rate, time to disease progression on radiographic scans or death, and overall survival. At the 2019 ASCO GU, researchers presented interim efficacy and safety findings from cohorts A, B and C. Cohort A: “Keynote-365 cohort a: Pembrolizumab (pembro) plus olaparib in docet
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