First-line (1L) nivolumab (N) + ipilimumab (I) + chemotherapy (C) vs C alone in patients (pts) with metastatic NSCLC (mNSCLC) from CheckMate 9LA: 4‑y clinical update and outcomes by tumor histologic subtype (THS).

David Paul Carbone The Ohio State University Comprehensive Cancer Center, Columbus, OH info_outline David Paul Carbone, Tudor-Eliade Ciuleanu, Michael Schenker, Manuel Cobo-Dols, Stephanie Bordenave, Oscar Juan-Vidal, Juliana Janoski De Menezes, Niels Reinmuth, Eduardo Richardet, Ying Cheng, Hideaki Mizutani, Luis G. Paz-Ares, Shun Lu, Tom John, Xiaoqing Zhang, Nan Hu, David Balli, Vipul Baxi, Jaclyn Neely, Martin Reck

Authors David Paul Carbone The Ohio State University Comprehensive Cancer Center, Columbus, OH info_outline David Paul Carbone, Tudor-Eliade Ciuleanu, Michael Schenker, Manuel Cobo-Dols, Stephanie Bordenave, Oscar Juan-Vidal, Juliana Janoski De Menezes, Niels Reinmuth, Eduardo Richardet, Ying Cheng, Hideaki Mizutani, Luis G. Paz-Ares, Shun Lu, Tom John, Xiaoqing Zhang, Nan Hu, David Balli, Vipul Baxi, Jaclyn Neely, Martin Reck Organizations The Ohio State University Comprehensive Cancer Center, Columbus, OH, Institutul Oncologic Prof Dr Ion Chiricută and University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania, SF Nectarie Oncology Center, Craiova, Romania, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain, L’institut du Thorax, Nantes, France, Hospital Universitario La Fe, Valencia, Spain, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, Asklepios Lung Clinic, Munich-Gauting, Germany, IONC Instituto Oncológico De Córdoba, Córdoba, Argentina, Jilin Cancer Hospital, Changchun, Jilin, China, Saitama Cancer Center, Saitama, Japan, Hospital Universitario, 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China, Austin Hospital, Heidelberg, VIC, Australia, Bristol Myers Squibb, Princeton, NJ, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Bristol Myers Squibb Background: In CheckMate 9LA (NCT03215706), 1L N + I + C demonstrated durable survival benefit in pts with mNSCLC vs C alone. Here, we report updated efficacy and safety with a 4-y minimum (min) follow-up (f/u) as well as exploratory analyses of efficacy by THS, a known prognostic indicator for NSCLC. Methods: Adults with stage IV/recurrent NSCLC (no known sensitizing EGFR/ALK alterations) and ECOG PS ≤ 1 were randomized 1:1 to N 360 mg Q3W + I 1 mg/kg Q6W + 2 cycles of C (n = 361) or 4 cycles of C alone (n = 358). Pts were stratified by sex, PD-L1 (< 1% vs ≥ 1%), and histology (squamous [SQ] vs non-squamous [NSQ]). Maintenance pemetrexed was allowed in the C arm (NSQ NSCLC). Assessments included OS, PFS, ORR, safety, treatment (tx)-free interval (TFI; time from last study dose to start of first subsequent systemic tx or death), and efficacy by THS (solid, acinar, or other, per modified WHO classification). Results: At a min f/u of 47.9 mo (database lock, Feb 2023; median f/u, 54.5 mo), N + I + C continued to provide long-term, durable OS benefit vs C in all randomized pts (HR, 0.74 [95% CI 0.63–0.87]; 4-y OS rates, 21% vs 16%, respectively). Similar clinical benefit was seen for N + I + C vs C across tumor PD-L1 or histology subgroups (table). In all pts treated with N + I + C (n = 358), median TFI was 2.2 mo, with 11% remaining tx-free and alive at 4y. In pts who discontinued all components of N + I + C due to tx-related adverse events (n = 61), 4-y OS rate was 41%; median TFI was 10.6 mo, with a 4-y TFI rate of 27%. In an exploratory analysis in pts with evaluable NSQ NSCLC tissue (n = 310; min f/u 36.1 mo), median OS was longer with N + I + C vs C in both solid (16.6 vs 9.3 mo) and acinar (18.7 vs 12.9 mo) THS. Updated efficacy by THS will be presented. No new safety signals were identified with longer f/u. Conclusions: With a 4-y min f/u, pts treated with N + I + C continued to derive long-term, durable efficacy benefit vs C regardless of tumor PD-L1 expression or histology, with greater magnitude of benefit in pts with tumor PD-L1 < 1% or SQ histology. Exploratory analyses suggested OS benefit with N + I + C vs C in both solid and acinar subtypes. Together, these data further reinforce the use of N + I + C as an efficacious 1L tx option for pts with mNSCLC. Clinical trial information: NCT03215706. Efficacy by PD-L1 expression and histology. PD-L1 < 1% PD-L1 ≥ 1% SQ NSQ All randomized N + I + C n = 135 C n = 129 N + I + C n = 204 C n = 204 N + I + C n = 115 Cn = 112 N + I + C n = 246 C n = 246 N + I + C n = 361 C n = 358 Median OS, mo 17.7 9.8 15.8 10.9 14.5 9.1 17.8 12.0 15.8 11.0 OS HR vs C (95% CI) 0.66 (0.50–0.86) - 0.74 (0.60–0.92) - 0.64 (0.48–0.84) - 0.80 (0.66–0.97) - 0.74 (0.63–0.87) - 4-y OS rate, % 23 13 21 16 20 10 22 19 21 16 4-y PFS rate, % 12 3 12 6 8 4 13 5 12 5 ORR, n (%) 42 (31) 26 (20) 87 (43) 56 (27) 56 (49) 35 (31) 81 (33) 55 (22) 137 (38) 90 (25) Median duration of response, mo 17.5 4.3 11.8 5.6 10.8 3.9 20.0 7.1 12.4 5.6 Responders with ongoing response ≥ 4 y, % 29 0 24 15 17 6 30 16 25 12

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