Inhibitors of programmed death 1 (PD-1) and its ligand PD-L1 are effective for treatment of recurrent, advanced urothelial cancer. Data from KEYNOTE-052 showed first-line pembrolizumab (anti–PD-1) had antitumor activity with an acceptable safety profile in cisplatin-ineligible patients (pts) with advanced urothelial cancer. This suggests pembrolizumab may be effective as first-line treatment, a setting in which only 50% of pts can receive the current standard-of-care, cisplatin-based chemotherapy. A randomized, open-label, phase 3 study in pts with advanced urothelial carcinoma is assessing first-line pembrolizumab ± chemotherapy versus chemotherapy (KEYNOTE-361; NCT02853305).
Approximately 990 pts with histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma will be randomly assigned 1:1:1 to pembrolizumab 200 mg every 3 weeks (Q3W), pembrolizumab + chemotherapy (investigator’s choice of cisplatin [70 mg/m2 Q3W] plus gemcitabine [1000 mg/m2 on days 1 and 8 Q3W] OR carboplatin [AUC 5 Q3W] plus gemcitabine if cisplatin ineligible), or chemotherapy alone. Pts must have measurable disease per investigator review (RECIST v1.1), an ECOG PS 0–2, received no prior systemic chemotherapy for advanced urothelial cancer, and provided a tumor biopsy. Treatment allocation will be stratified by chemotherapy (cisplatin or carboplatin) and PD-L1 expression (+ or –). Patients will be treated for 35 cycles of pembrolizumab (pembrolizumab arms only), or until progressive disease or unacceptable adverse events. The primary end points are progression-free survival (RECIST v1.1 per blinded independent central review) and overall survival, assessed in all patients and PD-L1+ patients. Secondary end points are objective response rate and safety. Efficacy will be compared for pembrolizumab versus chemotherapy and pembrolizumab + chemotherapy versus chemotherapy. Patient accrual is ongoing; 1 interim efficacy analysis is planned.
Clinical trial identification
NCT02853305; July 29, 2016
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
T. Powles: Received research funding from Merck, AstraZeneca and Roche; honoraria and travel expense reimbursement from Pfizer, Merck, AstraZeneca, Roche, and Novartis. J.E. Gschwend: Served as advisor for and received honoraria and reimbursements for travel expenses from Bayer, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and Roche. Y. Loriot: Served as advisory board member for Astellas, Janssen, Roche, MSD, AstraZeneca; received research funding and honoraria from Sanofi and received reimbursement for travel expenses from Roche, MSD, Janssen, and AstraZeneca. J. Bellmunt: Received honoraria from Merck, Genentech, Pfizer, and AstraZeneca. C. Vulsteke: Served as consultant/advisor to Novartis, Leo Pharma, and Roche and received reimbursement for travel expenses from Novartis, Pfizer, and Roche. M. Abdelsalam: Have been an advisory board member for Pfizer, Merck, Novartis, served on speakers\' bureaus for Pfizer and Roche, received honoraria from Pfizer, Merck, Roche, Novartis, AstraZeneca, and been reimbursed for travel expenses by Amgen, Roche, AstraZeneca. M. Fleming: Served as advisory board member and as speakers\' bureau member for Genentech. M. Markus: Served as consultant/advisor for Biotheranostics. D. Feng: Employed by and own stock in Merck & Co., Inc. C. Poehlein: Employed by Merck & Co., Inc. A. Alva: Received honoraria from and served as consultant/advisor to Eisai and have received research funding from BIND Biosciences, Bristol-Myers Squibb, Genentech, Novartis, and Oncogenex. All other authors have declared no conflicts of interest.