A phase II, randomized study of nivolumab (nivo) or nivo plus BMS-986205 with or without intravesical Bacillus Calmette-Guerin (BCG) in BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC): CheckMate 9UT.


Immune checkpoint inhibitors, including nivo (anti–PD-1), have demonstrated favorable tolerability and efficacy profiles, ushering in a new treatment (tx) paradigm for advanced bladder cancer (advBC). However, an unmet need exists for new effective tx options in earlier stages of disease, specifically for patients (pts) with BCG-unresponsive, high-risk NMIBC. Increased IDO and PD-L1 expression in NMIBC tumors (Inman, et al. Cancer 2007; Hudolin, et al. Anticancer Res 2017), support the combination of anti–PD-1 and IDO1 inhibition in NMIBC. BMS-986205, a selective, potent, once-daily IDO1 inhibitor that works early in the IDO1 pathway, has demonstrated clinical activity in combination with nivo in pts with immunotherapy-naive advBC who received ≥ 1 prior line of therapy (objective response rate, 37%; Tabernero, et al. J Clin Oncol 2018;36(suppl) [abstr 4512]). These findings provide a rationale for investigation of nivo + BMS-986205 ± intravesical BCG therapy in BCG-unresponsive high-risk NMIBC. Here we describe a phase 2, randomized, open-label study assessing the safety and efficacy of nivo ± BMS-986205 ± intravesical BCG in pts with BCG-unresponsive, high-risk NMIBC.


Pts aged ≥ 18 years with BCG-unresponsive (per February 2018 FDA guidance), high-risk NMIBC, defined as carcinoma-in-situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions, will be enrolled. Pts must have urothelial carcinoma as the predominant histological component (>50%). Key exclusion criteria include locally advanced or metastatic BC, upper urinary tract disease within 2 years, prostatic urethral disease within 1 year, and prior immunotherapy. Using a novel adaptive-type design, pts will be randomized to 1 of 4 tx arms with nivo ± BMS-986205 ± BCG. Primary endpoints include proportion of pts with CIS with complete response (CR), duration of CR in pts with CIS, and event-free survival for all pts without CIS. Secondary endpoints are progression-free survival and safety. This global study in 13 countries is underway, with a target enrollment of 436 pts. Clinical trial information: NCT03519256.

DOI: 10.1200/JCO.2019.37.7_suppl.TPS493 Journal of Clinical Oncology 37, no. 7_suppl Published online February 26, 2019.

Noah M. Hahn, Sam S. Chang, Maxwell Meng, Neal D. Shore, Badrinath R. Konety, Gary D. Steinberg, Juergen E. Gschwend, Hiroyuki Nishiyama, Juan Palou Redorta, John Arthur Taylor, Ayanbola Elegbe, Alexandre Lambert, Li Zhu, Yuko Ishii, Toshiki Maeda, Bradley Raybold, Gary Grossfeld, Bruce S. Fischer, Mark Rutstein, Alfred Witjes 

Johns Hopkins University School of Medicine, Baltimore, MD; Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN; Department of Urology, University of California, San Francisco, CA; Carolina Urologic Research Center, Myrtle Beach, SC; University of Minnesota, Minneapolis, MN; The University of Chicago Medical Center, Chicago, IL; Department of Urology, Technical University of Munich, Munich, Germany; University of Tsukuba, Tsukuba, Japan; Department of Urology, Fundació Puigvert, Autonomous University of Barcelona, Barcelona, Spain; Department of Urology, University of Kansas Medical Center, Kansas City, KS; Bristol-Myers Squibb, Princeton, NJ; Department of Urology, Radboud University Medical Centre, Nijmegen, Netherlands