Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Patients With Untreated Inoperable or Metastatic Urothelial Cancer (CheckMate901)

Bristol-Myers Squibb + Ono Pharmaceutical Co. Ltd
Study Design: 
This is a Phase III, 4-armed randomized parallel assessment clinical trial with experimental and comparator arms that includes both cisplatin eligible and ineligible patients with first line unresectable or metastatic urothelial cancer. The trial compares the combination of nivolumab and ipilumimab to nivolumab plus cisplatin and gemcitabine followed by nivolumab only versus gemcitabine and cisplatin or gemcitabine and carboplatin.
The purpose of this study is to determine whether immunotherapy with a PD-1 inhibitor, Nivolumab, in combination with ipilimumab, a CTLA-4 inhibitor, or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating patients with previously untreated inoperable or metastatic urothelial cancer.
PFS and OS
Nivolumab has been evaluated in metastatic urothelial carcinoma after platinum therapy in the CheckMate 275 trial. This was a multicenter, single-arm, phase 2 trial in which 270 patients received nivolumab and 265 were evaluated for activity. Median follow-up for overall survival was 7 months. Confirmed objective response was achieved in 52 (19.6%) of 265 patients. Confirmed objective response was observed in 23 (28.4%) of 81 patients with PD-L1 expression > 5%, 29 (23.8%) of 122 patients with PD-L1 expression > 1%, and 23 (16.1%) of 143 patients with PD-L1 expression <1% PD-L1 expression. In this study, nivolumab monotherapy provided meaningful clinical benefit, irrespective of PD-L1 expression, and was associated with an acceptable safety profile in previously treated patients with metastatic or surgically unresectable urothelial carcinoma. The CTLA-4 inhibitor ipilimumab has clinical activity in melanoma as a single agent or in combination with the nivolumab, establishing the paradigm for exploring the combination in urothelial carcinoma (9). Additionally, some evidence has suggested that ipilimumab has biologic activity in urothelial cancer (10).