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Background Immunotherapy with or without chemo has improved survival vs chemo in 1L aNSCLC. NIVO + chemo showed encouraging activity in a phase 1 study in this setting. CheckMate 227 is a multi-part, randomized, open-label, phase 3 study evaluating NIVO-based regimens vs chemo. We present final results from Part 2, which evaluated NIVO + chemo vs chemo in 1L aNSCLC. Methods Pts (N = 755) with chemo-naive, stage IV or recurrent NSCLC, ECOG PS 0–1, and no sensitizing EGFR/ALK alterations were randomized 1:1 to receive every 3 weeks NIVO 360 mg + chemo or chemo. Pts were stratified by histology (squamous [SQ] vs non-squamous [NSQ]), sex, and PD-L1 expression ( Results Baseline characteristics were generally balanced. Minimum follow-up was 19.5 mo. In pts with NSQ NSCLC, no statistically significant improvement in OS was seen with NIVO + chemo vs chemo (HR, 0.86 [95.62% CI, 0.69–1.08; P=0.1859]); median OS was 18.8 mo vs 15.6 mo; 12-mo OS rates were 67.3% vs 59.2%. HR for OS was 0.81 (95% CI, 0.67–0.97) in all randomized pts; 0.69 (95% CI, 0.50–0.97) in pts with SQ NSCLC. Progression-free survival and objective response rates favored NIVO + chemo in NSQ, SQ, and all randomized pts (table). Grade 3–4 tx-related adverse events occurred in 45% and 35% of all pts treated with NIVO + chemo and chemo, respectively.TableLBA3 Efficacy outcomes with 1L NIVO + chemo vs chemo in pts with NSQ NSCLC, SQ NSCLC, and in all randomized ptsTableNSQ NSCLCSQ NSCLCAll Randomized PtsNIVO + chemoChemoNIVO + chemoChemoNIVO + chemoChemon=270n = 273n=107n = 105n=377n = 378OSEvents, n (%)156 (57.8)164 (60.1)68 (63.6)75 (71.4)224 (59.4)239 (63.2)Median, mo18.815.618.312.018.314.7HR (95% CI)0.86 (0.69–1.08)aP = 0.18590.69 (0.50–0.97)0.81 (0.67–0.97)12-mo OS rate, %67.359.266.148.566.956.2PFSEvents, n (%)187 (69.3)200 (73.3)79 (73.8)82 (78.1)266 (70.6)282 (74.6)Median, mo8.75.87.14.48.45.5HR (95% CI)0.67 (0.55–0.82)0.51 (0.37–0.70)0.62 (0.52–0.73)12-mo PFS rate, %39.525.731.79.337.321.3Objective response rate, n (%)130 (48.1)80 (29.3)64 (59.8)34 (32.4)194 (51.5)114 (30.2)a95.62% CI Conclusion CheckMate 227 Part 2 did not meet the primary endpoint of OS for NIVO + chemo vs chemo in NSQ NSCLC. Descriptive analyses showed longer OS with NIVO + chemo in all randomized pts and SQ NSCLC. No new safety signals were observed. Clinical trial identification NCT02477826; Release date: June 23, 2015. Editorial acknowledgement Writing and editorial assistance was provided by Namiko Abe, PhD, of Caudex, funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure L. Paz-Ares: Honoraria (self): Roche, MSD, Lilly, Novartis, Boehringer Ingelheim, AstraZeneca, Amgen, Sanofi, Pharmamar, Pfizer, Bristol-Myers Squibb, Merck, Takeda, Celgene, Servier, Sysmex, Incyte, Ipsen, Adacap, Bayer, Blueprint; Leadership role: Altum Sequencing; Research grant / Funding (institution): MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb; Officer / Board of Directors: Genomica. T.E. Ciuleanu: Advisory / Consultancy: Astellas, Janssen, Bristol-Myers Squibb, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Lilly, AstraZeneca, MSD, Sanofi, Novartis, Servier, AD Pharma. A. Pluzanski: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche; Speaker Bureau / Expert testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche, Takeda; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche. A. Nagrial: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche; Research grant / Funding (institution): Astra Zeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche. R. Kowalyszyn: Advisory / Consultancy: Astellas, Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, MSD, Novartis; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Lilly, MSD, Pfizer, Roche. C. Audigier-Valette: Honoraria (self): AbbVie, Pfizer; Honoraria (institution): Roche, MSD, Bristol-Myers Squibb, AstraZeneca; Advisory / Consultancy: Roche, MSD, Bristol-Myers Squibb, AstraZeneca, AbbVie, Pfizer. Y-L. Wu: Honoraria (self): AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche; Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim, BMS, Roche; Non-remunerated activity/ies: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche. H. Borghaei: Honoraria (self): University of Pennsylvania, CAR T Program, Takeda [Data and Safety Monitoring Board]; Advisory / Consultancy: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Takeda, Huya Bio, GLG; Research grant / Funding (self): Millennium, Merck/Celgene, Bristol-Myers Squibb/Lilly. M.D. Hellmann: Advisory / Consultancy: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, Syndax, Shattuck Labs, Immunai, Nektar, Blueprint Medicines; Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bristol-Myers Squibb, AstraZeneca; Shareholder / Stockholder / Stock options: Shattuck Labs, Immunai. J. Brahmer: Advisory / Consultancy: Bristol-Myers Squibb, AstraZeneca, Genentech, Merck, Amgen. M. Reck: Honoraria (self): AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche; Advisory / Consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Ramalingam: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Roche/Genentech, Loxo, Tesaro, Merck, Daichi; Advisory / Consultancy: Amgen, AbbVie, Lilly, Genentech, Takeda; Research grant / Funding (institution): Bristol-Myers Squibb, Amgen, AstraZeneca, Takeda, Advaxis, Tesaro, Merck. L. Zhang: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: AstraZeneca, Bristol-Myers Squibb, MSD, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, Pfizer, Henrui Pharm. P. Bhagavatheeswaran: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F.E. Nathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. K.J. O'Byrne: Advisory / Consultancy: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim, Novartis, Teva, Janssen-Cilag, Natera; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim, Janssen-Cilag, Mundipharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim; Shareholder / Stockholder / Stock options: Carp Pharmaceuticals, Carpe Vitae Phaemaceuticals; Licensing / Royalties: Various patents issues with licensee as listed. Queensland University of Technology and Trinity College Dublin. All other authors have declared no conflicts of interest.

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 3mg/kg Q2W + IPI 1mg/kg Q6W, NIVO 240mg Q2W, or histology-based chemo; pts with PD-L1 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 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 Clinical trial identification NCT02477826; Release date: June 23, 2015. Editorial acknowledgement Writing and editorial assistance was provided by Namiko Abe, PhD, of Caudex, funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure S. Peters: Advisory / Consultancy, Research grant / Funding (institution): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bioinvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, M. S.S. Ramalingam: Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Personal fees, advisory board: Amgen; Honoraria (self), Advisory / Consultancy, Personal fees, advisory board: AbbVie; Honoraria (self), Advisory / Consultancy, Personal fees, advisory board: Lilly; Honoraria (self), Advisory / Consultancy, Personal fees, advisory board: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Personal fees, advisory board: Takeda; Honoraria (self), Personal fees: Loxo; Research grant / Funding (institution): Advaxis; Honoraria (self), Research grant / Funding (institution), Personal fees: Tesaro; Honoraria (self), Research grant / Funding (institution), Personal fees: Merck; Honoraria (self), Research grant / Funding (self), Personal fees: AstraZeneca. L. Paz-Ares: Advisory / Consultancy, Advisory board: Genomica; Honoraria (self), Personal fees: Lilly, MSD, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer, Ipsen, Adacap, Sanofi, Bayer, Blueprint, Bristol-Myers Squibb; Advisory / Consultancy, Scientific advice/speaker: Lilly, MSD, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer, Ipsen, Adacap, Sanofi, Bayer, Blueprint, Bristol-Myers Squibb; Officer / Board of Directors, Co-founder and board member: Altum Sequencing; Research grant / Funding (institution), Grant: MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb. H. Sakai: Research grant / Funding (institution), Grant: Ono Pharmaceutical Company, Bristol-Myers Squibb Company, AstraZeneca, Chugai Pharmaceutical Company, Merck & Co, Merck KGaA; Honoraria (self), Personal fees: Ono Pharmaceutical Company, Bristol-Myers Squibb Company, AstraZeneca, Chugai Pharmaceutical Company, Merck & Co, Merck KGaA. A. Vergnenegre: Honoraria (self), Advisory / Consultancy, Personal fees, travels for medical conferences and fees for consulting: Bristol-Myers Squibb, MSD, AstraZeneca. M. Reck: Honoraria (self), Advisory / Consultancy, Honoraria for lectures and consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. H. Borghaei: Research grant / Funding (institution): Millennium, Merck/Celgene, Bristol-Myers Squibb/Lilly; Advisory / Consultancy: BMS, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Takeda, Huya Bio, Diiachi; Advisory / Consultancy, Data Safety and Monitoring Board: University of Pennsylvania, CAR T Program; Takeda; Full / Part-time employment: Fox Chase Cancer Center. J.R. Brahmer: Advisory / Consultancy, Research grant / Funding (institution), Grant, advisory board: Bristol-Myers Squibb; Advisory / Consultancy, Advisory board: AstraZeneca, Genentech, Merck. K.J. O'Byrne: Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory board and speaker bureau fees and travel grants to national and international meetings: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim; Advisory / Consultancy, Advisory board: Novartis, Teva, Natera; Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory board and speaker bureau fees: Janssen-Cilag; Speaker Bureau / Expert testimony, Speaker bureau: Mundipharma; Shareholder / Stockholder / Stock options, Shareholder: Carp Pharmaceuticals, Carpe Vitae Pharmaceuticals; Licensing / Royalties, Various patents issues with licensee as listed: Queensland University of Technology and Trinity College Dublin. W.J. Geese: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. P. Bhagavatheeswaran: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F.E. Nathan: Full / Part-time employment: Bristol-Myers Squibb. M.D. Hellmann: Advisory / Consultancy, Fees for consulting: Genentech, Merck, Novartis, Janssen, Mirati, Syndax, Nektar, Blueprint Medicines; Advisory / Consultancy, Research grant / Funding (institution), Research grant to institution, fees for consulting and travel (grant, personal fees, non-financial support): Bristol-Myers Squibb; Advisory / Consultancy, Fees for consulting and travel: AstraZeneca; Advisory / Consultancy, Fees for consulting and equity: Shattuck Labs, Immunai; Licensing / Royalties, Patent filed by Memorial Sloan Kettering related to the use of tumor mutation burden to predict response to immunotherapy: PGDx. All other authors have declared no conflicts of interest.