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

Abstract

Background: 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%. Methods: 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 3 mg/kg Q2W+ IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or histology‐ based chemo; pts with PD‐L1 < 1% (n=550) were randomized 1:1:1 to NIVO 3 mg/kg Q2W+ IPI 1 mg/kg Q6W, NIVO 360 mg 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. Results: 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. Conclusions: CheckMate 227 met its primary endpoint of significantly improved OS with NIVO + IPI vs chemo in 1L advanced NSCLC with PD‐L1 ≥ 1%. OS was also improved with NIVO + IPI in PD‐L1 <1% and in all randomized pts. Safety profile was consistent with previous reports in NSCLC. NIVO +IPI represents a new chemofree tx option for pts in 1L advanced NSCLC. (Table Presented) .