LBA4_PR - Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis

Part 1 of CheckMate 227 (NCT02477826), a phase III study in 1L NSCLC, has dual primary endpoints. The primary endpoint of progression-free survival (PFS) with NIVO + IPI vs chemo in patients (pts) with tumor mutational burden ≥ 10 mut/Mb was met, as reported previously. Here we present the primary endpoint of overall survival (OS) for NIVO + IPI vs chemo in pts with tumor PD-L1 expression ≥ 1%. Pts were chemo-naive, with stage IV or recurrent NSCLC without EGFR or known ALK alterations, ECOG PS 0–1. Pts with PD-L1 ≥1% (n=1189) were randomized 1:1:1 to NIVO 3mg/kg Q2W + IPI 1mg/kg Q6W, NIVO 240mg Q2W, or histology-based chemo; pts with PD-L1 < 1% (n=550) were randomized 1:1:1 to NIVO 3mg/kg Q2W + IPI 1mg/kg Q6W, NIVO 360mg Q3W + chemo, or chemo. Pts were stratified by histology in both populations. Pts were treated until disease progression, unacceptable toxicity, or for 2 y of immunotherapy. Baseline characteristics were balanced across tx arms. Minimum follow-up for the primary endpoint was 29.3mo. For pts with PD-L1 ≥ 1%, OS was significantly longer with NIVO + IPI vs chemo (HR 0.79, 97.72% CI: 0.65–0.96; P=0.007); PFS, objective response rates, and duration of response favored NIVO + IPI vs chemo. OS benefit was also observed in pts with PD-L1 < 1% and all randomized pts (Table). Prespecified analyses showed enhanced efficacy with NIVO + IPI relative to NIVO in PD-L1 ≥ 1% and relative to NIVO + chemo in PD-L1 < 1%. Grade 3–4 tx-related adverse event rates in all randomized pts were 33% with NIVO + low-dose IPI, 19% with NIVO, and 36% with chemo.Table: LBA4_PREfficacy outcomes with NIVO + IPI, NIVO, NIVO + chemo, and chemo in 1L advanced NSCLC with PD-L1 ≥ 1%, PD-L1 < 1%, and in all randomized pts in CheckMate 227 part 1Table: LBA4_PRPD-L1 ≥ 1%NIVO + IPI n=396Chemo n=397NIVOa n=396Median OS, mo (95% CI) HR vs chemo (97.72% CI) P value 1-year OS rate, % 2-year OS rate, %17.1 (15.0–20.1) 0.79 (0.65–0.96) P=0.007 63 4014.9 (12.7–16.7) - - 56 3315.7 (13.3–18.1) 0.88 (0.75–1.04)b - 57 36Median PFS, mo (95% CI) HR vs chemo (95% CI)5.1 (4.1–6.3) 0.82 (0.69–0.97)5.6 (4.6–5.8) -4.2 (3.0–5.3) 0.99 (0.84–1.17)Objective response rate, n (%) Median duration of response, mo (95% CI)142 (35.9) 23.2 (15.2–32.2)119 (30.0) 6.2 (5.6–7.4)109 (27.5) 15.5 (12.7–23.5)PD-L1 < 1%NIVO + IPI n=187Chemo n=186NIVO + chemoc n=177Median OS, mo (95% CI) HR vs chemo (95% CI) 1-year OS rate, % 2-year OS rate, %17.2 (12.8–22.0) 0.62 (0.48–0.78) 60 4012.2 (9.2–14.3) - 51 2315.2 (12.3–19.8)