BMS-986012 (anti-fucosyl-monosialoganglioside-1 [fuc-GM1]) with carboplatin + etoposide + nivolumab (CE/NIVO) as first-line (1L) therapy in extensive-stage small cell lung cancer (ES-SCLC):Interim analysis (IA) of a randomized phase II study

BMS-986012, a first-in-class, fully human immunoglobulin G1, binds fuc-GM1 with high affinity and specificity, and induces immune-mediated tumor cell death. BMS-986012 has shown preliminary antitumor activity and tolerability with NIVO in SCLC, in which fuc-GM1 is often highly expressed. Here we report a prespecified IA from a phase II study of BMS-986012 + CE/NIVO (Arm A) vs CE/NIVO (Arm B) as 1L ES-SCLC treatment (Tx).<br/><br/>Methods: Eligible patients (pts) were randomized 1:1 to four 21-day cycles of CE/NIVO ± BMS-986012 induction Tx, followed by up to 2 years (y) of NIVO ± BMS-986012 maintenance Tx. Primary endpoints were safety and progression-free survival (PFS) by blinded independent central review; overall survival (OS) was a secondary endpoint. The study was stratified by liver metastasis and ECOG performance status (PS).<br/><br/>Results: As of Sep 26, 2023, 132 pts had been randomized. Arms (both n = 66) were balanced for baseline characteristics, with overall median (m) age of 67 y (range 41–80); 89% of pts were White and 8% Asian; 73% were in Europe and 12% in North America. Liver metastases were present in 42% of pts, and 25%/75% had ECOG PS 0/1. The safety profile was similar between arms (Table). PFS did not significantly differ between arms: mPFS was 5.8 months (mo) (95% confidence interval [CI] 5.0–7.9) in Arm A vs 5.2 mo (95% CI 4.8–6.6) in Arm B (hazard ratio [HR] 0.89 [95% CI 0.57–1.40]; P = 0.61). mOS was 15.6 mo (95% CI 11.3–NA) in Arm A (23 deaths) vs 11.4 mo (95% CI 9.3–16.5) in Arm B (30 deaths), HR 0.80 (95% CI 0.46–1.40). At a later database lock (Feb 26, 2024), mPFS was 5.8 mo vs 5.1 mo (HR 0.81 [95% CI 0.53–1.23]), and mOS was 15.6 mo vs 11.4 mo (HR 0.71 [95% CI 0.44–1.16]), in Arm A vs Arm B, respectively.