A Phase 3 Randomized Study Of Neoadjuvant Chemotherapy (Nac) Alone Or In Combination With Nivolumab (Nivo) +/- Bms-986205 In Cisplatin-Eligible Muscle Invasive Bladder Cancer (Mibc).

TPS4587 Background: Immuno-oncology (IO) therapies have revolutionized the treatment (tx) of pts with advanced bladder cancer (advBC). For pts with cisplatin-eligible MIBC, the recommended tx regimen is cisplatin-based NAC prior to radical cystectomy (RC). However, since only ≈ 30% of pts achieve a pathologic complete response (pCR) translating to improved long-term outcomes with approved regimens, new therapies are needed. PD-L1 expression is associated with aggressive BC and has been shown to increase in BC after NAC, suggesting that the PD-1/PD-L1 axis is a valid therapeutic target. Additionally, expression of indoleamine 2,3-dioxygenase (IDO) is higher in BC than in normal bladder tissue and is associated with advanced disease and poor clinical outcome. BMS-986205, a selective, potent, once-daily oral IDO1 inhibitor that works early in the IDO1 pathway to reduce kynurenine production, has demonstrated clinical activity in combination with NIVO (anti–PD-1) in pts with IO tx–naive advBC who had ≥ 1 prior line of therapy (ORR, 37%). Taken together, these data provide a rationale for investigating NAC + NIVO + BMS-986205 in MIBC. Here we describe a randomized, partially blinded, phase 3 study evaluating the efficacy and safety of NAC ± NIVO ± BMS-986205 followed by RC and continued IO tx in pts with MIBC (NCT03661320). Methods: Pts aged ≥ 18 years with previously untreated MIBC (clinical stage T2-T4a, N0, M0), creatinine clearance ≥ 50 mL/min, and predominant UC histology who are eligible for cisplatin-based NAC and RC will be enrolled. Pts with evidence of positive lymph node; metastatic BC; or prior systemic therapy, radiotherapy, or surgery for BC other than TURBT are not eligible. Pts will be randomized to receive NAC (gemcitabine/cisplatin; arm A), NAC + NIVO + oral placebo (arm B), or NAC + NIVO + BMS-986205 (arm C) followed by RC (all arms); arms B and C will receive continued IO tx. Primary endpoints include pCR after neoadjuvant tx and event-free survival (arms C vs A; arms B vs A). Secondary endpoints are overall survival and safety. This global study in 28 countries began accrual in Nov 2018 and has a target enrollment of 1200 pts. Clinical trial information: NCT03661320.