OA11 First-Line Nivolumab + Ipilimumab in Asian Patients With Advanced NSCLC and High TMB (≥10 mut/Mb): Results From CheckMate 227

CheckMate 227 (NCT02477826), a randomized, open-label, multipart, phase 3 study, demonstrated significant progression-free survival (PFS) benefit with first-line nivolumab + ipilimumab versus histology-based, platinum-doublet chemotherapy (PT-DC) in patients with advanced non-small cell lung cancer (NSCLC) and high tumor mutational burden (TMB; ≥10 mutations/megabase [mut/Mb]). Safety was manageable and consistent with prior reports for nivolumab + low-dose ipilimumab. Here we report efficacy and safety of nivolumab + ipilimumab versus PT-DC in the Asian subpopulation from CheckMate 227. Patients with chemotherapy-naïve, histologically confirmed stage IV/recurrent NSCLC, ECOG performance status 0–1, and no known sensitizing EGFR/ALK alterations were randomized 1:1:1 to receive nivolumab + ipilimumab, nivolumab, or PT-DC (tumor programmed death ligand 1 [PD-L1] expression ≥1%) or 1:1:1 to nivolumab + ipilimumab, nivolumab + PT-DC, or PT-DC (tumor PD-L1 expression <1%). Nivolumab + ipilimumab was administered at nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Patients were treated until disease progression or unacceptable toxicity, for up to 2 years. TMB was determined from tumor tissue by FoundationOne CDx™ assay. A co-primary endpoint was PFS with nivolumab + ipilimumab versus PT-DC in patients with TMB ≥10 mut/Mb. Patients enrolled from Japan, South Korea, and Taiwan were included in the Asian subpopulation. Baseline characteristics of the Asian subpopulation (n=357) were similar to the global population (N=1739), with the exception that there were proportionally fewer female patients in the Asian subpopulation (22% versus 32%). Minimum follow-up was 11.2 months. In Asian patients with high TMB (n=53), nivolumab + ipilimumab (n=21) had improved efficacy versus PT-DC (n=32) with a 66% reduction in the risk of progression/death (HR 0.34 [95% CI 0.15–0.75]). One-year PFS rates were 64% with nivolumab + ipilimumab versus 17% with PT-DC. Objective response rates were 76% with nivolumab + ipilimumab versus 22% with PT-DC. Median duration of response was not reached with nivolumab + ipilimumab versus 4.2 months with PT-DC. Grade 3–4 treatment-related adverse events (TRAEs) were reported in 40% of patients with nivolumab + ipilimumab versus 37% with PT-DC. Any grade TRAEs leading to discontinuation occurred in 22% of patients treated with nivolumab + ipilimumab versus 12% with PT-DC. The results of this Asian subpopulation analysis are consistent with the CheckMate 227 global population. First-line nivolumab + ipilimumab demonstrated improved efficacy compared with chemotherapy and a manageable safety profile in Asian patients with advanced NSCLC and TMB ≥10 mut/Mb.