Presentation Authors: Jason Luke*, Chicago, IL, Josep Tabernero, Barcelona, Spain, Karen Gelmon, Vancouver, Canada, Andrea Varga, Villejuif, France, Victor Moreno, Madrid, Spain, Jayesh Desai, Ben Markman, Melbourne, Australia, Carlos Gomez-Roca, Toulouse, France, Filippo De Braud, Milan, Italy, Sandip Patel, La Jolla, CA, Matteo Carlino, Sydney, Australia, Lillian Siu, Toronto, Canada, Giuseppe Curigliano, Milan, Italy, Zhaohui Liu, Yuko Ishii, Megan Wind-Rotolo, Paul Basciano, Alex Azrilevich, Princeton, NJ, Anthony Joshua, Sydney, Australia
Introduction: Nivolumab (nivo; anti-PD-1) has shown durable responses and manageable safety (ORR, 19.6%; gr 3-4 treatment-related AEs [TRAEs], 18%) in advanced bladder cancer (advBC [Sharma et al. Lancet Oncol 2017]), but prolonging survival in more pts requires additional approaches to overcome tumor evasion mechanisms. IDO1 allows tumor escape through kynurenine (KYN) production, which stimulates regulatory T cells and suppresses effector T-cell proliferation. Anti-PD-1 can upregulate IDO1, supporting the rationale for combining nivo with an IDO1 inhibitor. BMS-986205 is a selective, potent, once-daily (QD), oral IDO1 inhibitor that works early in the IDO1 pathway to reduce KYN. BMS-986205 + nivo showed favorable safety and efficacy in heavily pretreated pts with select solid tumors (Luke et al. SITC 2017; NCT02658890). Updated safety across all tumor cohorts and efficacy in immuno-oncology (I-O)-naive advBC are reported.
Methods: Dose-escalation methods of this phase 1/2a, open-label study were previously described (Siu et al. AACR 2017); pts in expansion received BMS-986205 100 or 200 mg QD + nivo 240 mg IV Q2W or 480 mg IV Q4W. Objectives included safety and ORR (includes unconfirmed responses).
Results: As of Mar 2018, 516 pts received BMS-986205 + nivo; 45% had â‰¥2 prior regimens. TRAEs occurred in 57% of pts (gr 3-4, 12%), the most common were fatigue (15%) and nausea (12%); 19 pts (4%) discontinued (DC) due to TRAEs, and 3 ( < 1%) died due to a TRAE (myocarditis, Stevens-Johnson syndrome, hepatic failure). In all treated pts and in the advBC cohort (n=30), the frequency and severity of TRAEs and rate of DC due to TRAEs were lower with BMS-986205 100 vs 200 mg. Among the 27 pts with I-O-naive advBC, ORR was 37% (3 CR, 7 PR) and DCR was 56% (median duration of follow-up, 24 wk). ORR and DCR in select I-O-naive advBC pt subgroups are shown (Table). Durable responses were observed regardless of PD-L1 expression.
Conclusions: BMS-986205 + nivo was well tolerated in heavily pretreated pts, and tolerability was improved with the 100-mg BMS-986205 dose. Preliminary evidence of efficacy was observed in advBC, including I-O-naive pts with liver and other visceral metastases, supporting further evaluation of BMS-986205 + nivo.
Source of Funding: The study was supported by Bristol-Myers Squibb. Writing and editorial assistance was funded by Bristol-Myers Squibb.