As a result of promising data from its Phase Ib/II KEYNOTE-365 trial, Merck has announced three new Phase III trials into the safety and efficacy of Keytruda (pembrolizumab) for patients with metastatic castration-resistant prostate cancer.
There will be one Phase III trial for each of the three cohorts of the KEYNOTE-365 study – Lynparza (olaparib), docetaxel and prednisone and enzalutamide.
Merck chief medical officer, senior vice-president and head of global clinical development Dr Roy Barnes said: “At the core of our research program is a commitment to investigate the potential of Keytruda– both as combination and monotherapy – to serve as a foundational treatment, especially for cancers where additional therapies are needed.
“These promising data presented at American Society of Clinical Oncology Genitourinary Cancers Symposium coupled with the significant unmet medical need in patients with metastatic castration-resistant prostate cancer, propelled us to initiate three new Phase III trials to further evaluate these Keytruda combination regimens.”
The primary endpoints of the Phase Ib/II trial were safety, prostate specific antigen (Psa ) response rate and overall response rate. The secondary endpoints include radiographic progression-free survival (rPFS) and overall survival (OS ). Across all three cohorts, the safety profile of the combination therapy was consistent with the drugs alone for mCRPC.
Cohort A, the combination of Keytruda and Lynparza, achieved 14% PSA response rate in patients with measurable disease and the median time for PSA progression was 15.3 weeks for the same patient group. Overall response rate was 7%, as was the partial response rate.
Median rPFS was 4.7 months and 48% of participants had achieved rPFS at six months. OS was 13.5 months with six months OS reaching 73%.
PSA response rate for cohort B, Keytruda combined with docetaxel and prednisone, was 22% in measurable disease patients and PSA progression was achieved over a median of 24.1 weeks. Overall and partial response rate were both 14%.
Median rPFS was 8.3 months with 79% achieving rPFS at 6 months; Median OS was not reached at the time of analysis, but six month OS for the participants was 96%.
For cohort C, the combination of Keytruda and enzalutamide, PSA response rate in patients with measurable disease was 40% and PSA progression was 18.4 weeks for that group. Overall response rate was 20%, complete response rate was 8% and partial response rate was 12%.
Median rPFS was 6.1 months, with 59% of participants achieving rPFS at six months. Median OS was not available at time of analysis, but 91% had achieved OS at six months.