BMS-986205, an indoleamine 2,3-dioxygenase 1 inhibitor (IDO1i), in combination with nivolumab (NIVO): Updated safety across all tumor cohorts and efficacy in pts with advanced bladder cancer (advBC).

Abstract

Background: NIVO (anti-PD-1) has shown durable responses and manageable safety (ORR, 19.6%; grade 3-4 treatment-related AEs [TRAEs], 18%) in pts with advBC (Sharma P, 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 development of regulatory T cells and suppresses effector T-cell proliferation. Anti-PD-1 therapy can upregulate IDO1, supporting the rationale for combining NIVO with an IDO1i. BMS-986205 is a selective, potent, once-daily (QD), oral IDO1i that works early in the IDO1 pathway to reduce KYN production. BMS- 986205 + NIVO demonstrated a favorable safety profile and antitumor activity in heavily pretreated pts with select solid tumors (Luke J, et al. SITC 2017; NCT02658890). Updated safety across all tumor cohorts and efficacy in the advBC cohort are reported. Method(s): Dose-escalation methods of this phase 1/2a, open-label study were previously described; during expansion, pts received BMS-986205 100 or 200 mg QD + NIVO 240 mg IV Q2W or 480 mg IV Q4W. Objectives included safety and ORR by RECIST v1.1 (includes unconfirmed [u] responses). Prior IO therapy was permitted in the advBC cohort. Result(s): As of Dec 15, 2017, 434 pts received BMS-986205 + NIVO. TRAEs were reported in 51% of pts (grade 3-4, 12%), the most common being fatigue (13%) and nausea (10%); 16 pts (4%) discontinued due to TRAEs, and 1 pt died due to a TRAE (myocarditis). With a median follow-up of 17 wk (range, 4-53), the ORR among 29 pts with advBC was 34% (1 u CR, 9 PRs [1 u]), and the disease control rate (DCR) was 48%. Of 29 pts, 26 had no prior IO therapy; ORR in these pts was 38% (1 u CR, 9 PR [1 u]), and the DCR was 54%. ORR in pts with tumor PD-L1 >= 1% (Dako PD-L1 IHC 28-8 pharmDx assay; n = 15) vs < 1% (n = 11) was 47% vs 27%. Conclusion(s): BMS-986205 + NIVO was well tolerated, with a safety profile similar to that of NIVO monotherapy. Preliminary evidence of efficacy was observed in advBC, supporting further evaluation of BMS-986205 + NIVO. Updated data by dose and subgroup in the advBC cohort will be presented.