Background: In CheckMate 9LA (NCT03215706), 1L NIVO + IPI combined with 2 cycles of chemo was shown to provide survival benefit vs chemo alone in pts with metastatic NSCLC. Here, we report updated efficacy and safety with a 3-year minimum follow-up, as well as exploratory biomarker analyses from this study. Methods: Adults with stage IV or recurrent NSCLC, no known sensitizing EGFR/ALK alterations, and ECOG performance status ≤ 1 were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + 2 cycles of chemo (n = 361) or 4 cycles of chemo alone (n = 358). Pts were stratified by tumor PD-L1 expression, sex, and histology. Pts with non-squamous (NSQ) NSCLC in the chemo-alone arm could receive pemetrexed maintenance. Assessments included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). For all pts with NSQ NSCLC and with tissue evaluable for mutational analysis (n = 313), the FoundationOne CDxTM assay was used to identify mutant (mut) or wild type (wt) KRAS and STK11 genes. Exploratory assessments included evaluation of OS and PFS with NIVO + IPI + chemo vs chemo by mutation status and safety. Results: At a minimum follow-up of 36.1 mo (database lock: Feb 15, 2022), pts continued to derive long-term, durable OS benefit with NIVO + IPI + chemo vs chemo (HR, 0.74 [95% CI, 0.62–0.87]); 3-y OS rates were 27% vs 19%. Clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across most subgroups, including by PD-L1 expression level (Table) or histology. In an exploratory analysis in pts evaluable for mutations including KRAS and STK11, OS appeared to be improved with NIVO + IPI + chemo vs chemo (median OS, 16.3 vs 13.1 mo). Similar trends of prolonged OS with NIVO + IPI + chemo vs chemo were also seen in pts with or without KRAS mutation (median OS, mut: 19.2 vs 13.5 mo; wt: 15.6 vs 12.7 mo) or STK11 mutation (mut: 13.8 vs 10.7 mo; wt: 17.8 vs 13.9 mo), respectively. Additional efficacy outcomes will be presented. No new safety signals were identified with extended follow-up. Conclusions: With a 3-year minimum follow-up, 1L NIVO + IPI + chemo demonstrated long-term, durable efficacy benefit vs chemo in pts with metastatic NSCLC. Survival benefit of NIVO + IPI + chemo vs chemo was observed regardless of KRAS and STK11 mutation status. Clinical trial information: NCT03215706.