Nivolumab has shown promising efficacy and acceptable safety in an open-label, multicenter phase I/II study in patients (pts) with mUC after ≥1 prior platinum-based therapy (NCT01928394). Here we report updated efficacy and safety results for the overall population based on additional follow-up and outcomes by differing levels of PD-L1 expression.
Pts with mUC, unselected by PD-L1 expression status, received nivolumab 3 mg/kg IV every 2 wk until progression or discontinuation. Pts who met protocol criteria could continue treatment beyond progression and cross over to nivolumab + ipilimumab. Tumor PD-L1 membrane expression was assessed with Dako PD-L1 immunohistochemical staining. Primary endpoint: objective response rate (ORR; RECIST 1.1); other endpoints: safety, progression-free survival (PFS), overall survival (OS), and duration of response.
Of 78 treated pts (median age 65.5 years; range, 31–85), 52 received ≥2 prior therapies. At a minimum follow-up of 9 months, 23.1% of pts are on monotherapy and 23.1% switched to combination. Treatment discontinuation was mainly due to disease progression. PD-L1 was evaluable in 67 pts (86%). Table shows overall efficacy. In pts with PD-L1 expression ≥1% (n = 25) vs
Nivolumab showed encouraging efficacy and acceptable safety regardless of PD-L1 expression in previously treated, unselected pts with mUC.
|Parameter||Nivolumab (N = 78)|
|ORR (confirmed), % (95% CI)||24.4 (15.3–35.4)|
|Median PFS, mo (95% CI)||2.8 (1.5–5.9)|
|Median OS, mo (95% CI)||9.7 (7.3–16.2)|
|Median time to response, mo (SD)||1.5 (2.1)|
|Median duration of response, mo (95% CI)||Not estimable (NE) (9.9 − NE)|
Clinical trial identification
Legal entity responsible for the study
J.E. Rosenberg: Honoraria: UpToDate Consulting/Advisory: Boehringer Ingelheim, BMS, Janssen Oncology, J&J, Oncogenex, Lilly, Merck, Agensys, Roche/Genentech, Sanofi, AZ/MedImmune Research: Genentech, Oncogenex, Agensys, Mirati Therapeutics, Novartis . P. Bono: Honoraria: BMS, MSD, Orion Pharma, Pfizer, Novartis. J. Kim: Consulting/Advisory: Dendreon Research Funding: Immune Design. E. Calvo: Speakers' Bureau: Novartis Research Funding: Boehringer Ingelheim, Roche/Genetech, BMS, Novartis, PsiOxus, Janssen, Eisai, Abbvie, OncoMed, PharmaMar, Puma, Spectrum, Sanofi, Lilly, Pfizer, Merck, Nektar, Millenium Travel: Lilly, PsiOxus, Novartis. P.A. Ott: Consulting/Advisory: Amgen, BMS, Alexion Research Funding: BMS, Merck, Armo Biosciences, Astra Zeneca. F. de Braud: Consulting/Advisory: Tiziana Life Science, BMS, MSD, Servier, ELI Lilly, Merck Serono, GSK, Novartis Speakers' Bureau: BMS ELI Lilly, Roche, AccMed. M. Morse: Research Funding Precision Biologics BMS Onyx Eisai Lexicon MedImmune Advanced Accelerator Applications AlphaVax. D. Le: Honoraria: Merck Research Funding: Merck, BMS, Aduro. D. Jaeger: Consulting/Advisory: Roche, BMS, Bayer. E. Chan: Consulting/Advisory: Amgen, Lilly, Bayer, Taiho, EMD Serono Research Funding: Aduro, BMS, Millenium, Dekkun, Merrimack, Halozyme, Karyopharm, Boehring Ingelheim, Taiho. C. Harbison, C.S. Lin, M. Tschaika: Employment: BMS Stock: BMS. A. Azrilevich: Employment: BMS Stock: BMS Travel: 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.