Chemotherapy for platinum-resistant advanced mUC yields poor objective response rates (ORR) and overall survival (OS). Nivolumab (NIVO) recently showed promising efficacy and safety in the CheckMate 032 phase I/II study (NCT01928394) in this setting. The current larger study, CheckMate 275 (NCT02387996), investigated efficacy and safety of NIVO in patients (pts) with mUC or surgically unresectable locally advanced UC that progressed after platinum-based chemotherapy.
In this open-label, single-arm, phase II study, pts received NIVO 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. The primary endpoint was ORR confirmed by blinded independent review committee (RECIST 1.1). Outcomes were evaluated in all treated pts and by tumor programmed death-1 ligand 1 (PD-L1) expression (≥1% and ≥5%; Dako PD-L1 PharmDx). Biomarkers were analyzed for association between response, UC subtype (by The Cancer Genome Atlas), and immune gene signature expression.
At 7 mo of median follow-up, 24.4% of pts remain on therapy. Confirmed ORR was 19.6% (95% CI 15.0–24.9), and 16.1% (95% CI 10.5–23.1) in pts with low to no PD-L1 expression (Table). Median duration of response was not reached, with responses ongoing in 76.9% of responders. Median progression-free survival was 2.00 mo (95% CI 1.87–2.63); median OS was 8.74 mo (95% CI 6.05–not estimable). Grade 3–4 treatment-related adverse events occurred in 18% of pts (grade 5, 1%), mainly fatigue and diarrhea (2% each). Basal 1 UC subtype had the highest proportion of responders and strongest interferon gamma (IFNγ) gene signature expression. Quality of life was stable over time.
In this large study in advanced/unresectable UC, NIVO had clinically meaningful efficacy and a manageable safety profile. Efficacy benefit of NIVO was seen across all PD-L1 subgroups.
Clinical trial identification
Legal entity responsible for the study
Matthew D. Galsky
Funding for this study was provided by Bristol-Myers Squibb
M.D. Galsky: Stock ownership with Dual Therapeutics. Consulted with Genentech, Merck, Novartis, Astellas. Received research funding from BMS, Dendreon, Janssen, Novartis, and Merck. Intellectual properties with Mount Sinai school of Medicine. M. Retz: Received consulting and advising from BMS and Roche. A.O. Siefker-Radtke: Advisory board member of Janssen, Eisai, ad Genentech. Corporate sponsored research with Janssen, Millennium, Genentech, and AstraZeneca. A. Baron: Speakers bureau with Eli Lilly, Genetech, Merck, and BMS. Received research funding from BMS, Merck, and Genetech. A. Necchi: Consultant/advisor with Roche, MSD, Pierre Fabre, and Celgene. Research funding received from Millennium-Takeda, Amgen, and GSK. Travel and and expenses have been received from Roche, MSD, Pierre Fabre, Celgene, and Pfizer. J. Bedke: Consultant and advisor for Pfizer, Novartis, Bayer and Nektar. Research funding received from BMS, Novartis, Roche, and Immatics. Travel, accomodations, and expenses received from Bayer E.R. Plimack: Consultant/Advisor for Merck, Dendreon, Novartis, BMS, Pfizer, GSK, Acceleron Pharma, Genetech, Roche. Research fundin received from Merck, BMS, GSK, Accleron Pharma, Dendreon, Lilly, and AZ. Also have a US patent relating to health and research. D. Vaena: Site principal investigator at University of Iowa for industry trials: Bristol Myers Squibb, Argos Therapeutics, Glaxo Smith Kline, Bayer, Genentech Roche, Tekmira, Acerta, Tracon, M-O. Grimm: Honoraria received from Janssen Cilag, Sanofi, Astellas, Hexal, Bayer, Pfizer, Teva, Jenapharm, BMS, Pierre Fabre, and Novartis. Consulting role with GSK, Novartis, Pfizer, Bayer, BMS, and Sanofi. Research funding received from Novartis. S. Bracarda: Honoraria received from Pfizer, Novartis, Astellas, Bayer, and BMS. Advisory Board Member for Pfizer, Astellas, BMS, Novartis, Exelixis, and Roche. J. Arranz Arija: Consulthing or Advisory: Novartis, Jansen, Sanofi Travel, Accomodations, Expenses: Astellas S.K. Pal: Honoraria from Novartis, Medivation and Astellas Pharma, and receives consulting fees from Pfizer, Novartis, Aveo, Genentech, Exelixis, BMS, Astellas and GSK. A. Lambert: BMS employee and stock owner. S. Krishnan: Employment: Bristol-Myers Squibb Stock: Bristol-Myers Squibb A. Azrilevich: Employee and stockholder with BMS. Received travel and expenses from BMS. P. Sharma: compensation/leadership role and stock with Kite, Jounce, Evelo, and Neon. Consultant role with GSK. Amgen, BMS, and AZ. Own patient licensed to Jounce and patients licensed to BMS, Jounce Merck. Research as principal investigator for BMS, GSK, and AZ. All other authors have declared no conflicts of interest.