Trial Design: The key inclusion criteria for this phase III study include: (i) cisplatin-eligible and -ineligible patients with measurable disease, (ii) no prior systemic chemotherapy for unresectable/metastatic urothelial carcinoma, and (iii) evaluable tumor biopsy. Key exclusion criteria include: (i) active brain metastases, (ii) autoimmune disease, and (iii) prior treatment with drugs specifically targeting T-cell co-stimulation or checkpoint pathways. Cisplatin-eligible and -ineligible patients will be randomized 1:1 to arm A (nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks up to 4 doses, followed by nivolumab 480 mg every 4 weeks until disease progression or unacceptable toxicity) or arm B (gemcitabine-cisplatin or gemcitabine-carboplatin for up to 6 cycles). Additional cisplatin-eligible patients will be randomized to arm C (nivolumab 360 mg + gemcitabine-cisplatin every 3 weeks for up to 6 cycles, followed by nivolumab 480 mg) or arm D (gemcitabine-cisplatin for up to 6 cycles). Patients will be stratified by PD-1 ligand 1 status, cisplatin eligibility, and liver metastasis. The co-primary endpoints for this trial include overall and progression-free survival (OS and PFS) by blinded independent review committee in cisplatin-ineligible patients receiving nivolumab + ipilimumab vs standard of care, and PFS by blinded independent review committee in cisplatin-eligible patients receiving nivolumab + standard of care vs standard of care. Enrollment for CheckMate 901 began March 2017 in 30 countries worldwide, with a target of 897 patients.
Clinical trial information: NCT03036098
Speaker: Matt Galsky, Icahn School of Medicine at Mount Sinai Tisch Cancer Institute, New York, NY
Co-Authors: Thomas Powles, Shengting Li, Delphine Hennicken, Guru Sonpavde
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
1. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-322.
2. Sharma P, Callahan MK, Calvo E, et al. Efficacy and safety of nivolumab plus ipilimumab in previously treated metastatic urothelial carcinoma: First results from the phase I/II CheckMate 032 study. 2016 SITC Annual Meeting.