7128 - 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

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 29.3 mo. 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.Table: LBA4_PR

Efficacy outcomes with NIVO + IPI, NIVO, NIVO + chemo, and chemo in 1L advanced NSCLC with PD-L1 ≥ 1%, PD-L1 < 1%, and in all randomized pts in CheckMate 227 part 1

Study treatment only in PD-L1 ≥ 1% population;

95% CI for NIVO vs chemo;

study treatment only in PD-L1 < 1% population. Minimum follow-up for OS and PFS was 29.3 mo and for objective response rate, 28.3 mo.

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 chemo-free tx option for pts in 1L advanced NSCLC.

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: Genómica; 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.