LBA57 - Neoadjuvant nivolumab (N) + chemotherapy (C) in the phase III CheckMate 816 study: 3-y results by tumor PD-L1 expression

Background

In CheckMate 816, neoadjuvant N + C vs C significantly improved the primary endpoints of event-free survival (EFS) and pathological complete response (pCR) in patients with resectable NSCLC; 3-y EFS benefit with N + C vs C was also demonstrated. Here, we report clinical outcomes by baseline tumor PD-L1 expression.

Methods

Adults with stage IB (≥ 4 cm)–IIIA (AJCC v7) resectable NSCLC were randomized 1:1 to receive N 360 mg + C Q3W or C Q3W for 3 cycles. Exploratory analyses included EFS, overall survival (OS), pCR, major pathological response (MPR), surgical outcomes, and safety in patients with tumor PD-L1 ≥ 1% or < 1%.

Results

In patients with tumor PD-L1 ≥ 1% (N + C, 89; C, 89) and PD-L1 < 1% (78; 77), baseline characteristics were generally similar between PD-L1 subgroups and treatment arms. A higher proportion of patients with tumor PD-L1 < 1% had ECOG PS 1 (both arms). At database lock (14 Oct 2022; median follow-up, 41.4 mo), N + C showed improvement vs C across all efficacy endpoints in patients with tumor PD-L1 ≥ 1% (Table); 3-y EFS and OS rates were 72% vs 47% and 85% vs 66%, respectively. Similar efficacy benefit was seen in patients with tumor PD-L1 ≥ 1% and stage II–IIIA NSCLC (data to be presented). In patients with tumor PD-L1 < 1%, EFS, OS, pCR, and MPR also favored N + C vs C (Table); 3-y EFS and OS rates were 42% vs 39% and 71% vs 60%, respectively. Definitive surgery rates with N + C vs C were 84% vs 74% in patients with tumor PD-L1 ≥ 1% and 81% vs 77% in patients with tumor PD-L1 < 1%; R0 resection rates were 91% vs 82% and 79% vs 76%, respectively. Grade 3–4 treatment-related AE rates with N + C vs C were 34% vs 44% in patients with tumor PD-L1 ≥ 1% and 36% vs 34% in patients with tumor PD-L1 < 1%.

Conclusions

These exploratory analyses from CheckMate 816 reinforce the clinical benefit and manageable safety profile of neoadjuvant N + C in patients with resectable NSCLC regardless of tumor PD-L1 expression. Table: LBA57

Efficacy outcomes by tumor PD-L1 expression

NR, not reached.

Clinical trial identification

NCT02998528.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Mallika Kanwar, MD, PhD, Adel Chowdhury, PharmD, and Michele Salernitano of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

M. Provencio Pulla: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Takeda. P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Daiichi Sankyo, F-Star, G1, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface, LUNGevity; Financial Interests, Personal, Research Funding: AstraZeneca, BioNTech, BMS, Corvus, Kyowa, Novartis, and Regeneron and trial steering committee membership for AstraZeneca, Biontech, BMS, Corvus; Financial Interests, Personal, Member of Board of Directors: Mesothelioma Applied Research Foundation. J.D. Spicer: Financial Interests, Personal, Funding, Payments: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, CLS Therapeutics, Protalix Biotherapeutics, Merck, Roche Grants to Institution; Financial Interests, Personal, Other, consulting fees: AstraZeneca, BMS, CLS Therapeutics, Protalix Biotherapeutics, Merck, Roche Grants to Institution; Financial Interests, Personal, Other, honoraria: PeerView, BMS, AstraZeneca; Non-Financial Interests, Personal, Advisory Board: PUCC trial; Non-Financial Interests, Personal, Leadership Role: Industry chair for Canadian Association of Thoracic Surgeons. C. Wang: Financial Interests, Personal, Other, Support for attending meetings: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Leadership Role: Vice Chairmen of CSCO-Lung, Vice Chairmen of CSCO-Lung. S. Lu: Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui Beigene and Roche, Hansoh; Financial Interests, Personal, Other, consulting fees: AstraZeneca, Pfizer, BoehringerIngelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, Yuhan Corporation, PrIME Oncology, Menarini, InventisBio Co. Ltd., and Roche.; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Personal, Advisory Board: Roche, Regenron, AstraZeneca, Xcovery Holding; Financial Interests, Personal, Leadership Role: Chinese Lung Cancer Associate, CSCO. T. Mitsudomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Novartis, MSD, Ono, Pfizer, Amgen, Takeda, Eli Lilly, Merck Biopharma, Bayer; Financial Interests, Personal, Advisory Board: AsreaZeneca, Boehringer Ingelheim, Ono, Janssen; Financial Interests, Institutional, Local PI: Boehringer-Ingelheim, Chugai, MSD, Taiho, Daiichi Sankyo, Ono; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Leadership Role, Past President of International Association of Study for Lung Cancer: IASLC; Non-Financial Interests, Leadership Role: International Association for Study of Lung Cancer. M.M. Awad: Financial Interests, Personal, Other, Consultant: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, ArcherDX, Mirati, NextCure, Novartis, EMD Serono; Financial Interests, Institutional, Research Funding: AstraZeneca, Lilly, Genentech, Bristol-Myers Squibb. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, Glaxo Smith Kline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol-Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., Glaxo Smith Kline Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. S. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. S.J. Swanson: Financial Interests, Personal, Other, honoraria: Ethicon Payment to self. J.R. Brahmer: Non-Financial Interests, Other, medical writing: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Funding: Bristol Myers Squibb, AstraZeneca, Merck, Regeneron; Financial Interests, Personal, Other, Educational Lectures: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Johnson and Johnson, Sanofi, GSK, Society for the Immunotherapy of Cancer, LUNGevity Lung Cancer Research Foundation, Lung Cancer Foundation of America; Financial Interests, Personal, Writing Engagement, medical writing: Bristol Myers Squibb, Merck. K.M. Kerr: Financial Interests, Personal, Advisory Board, Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, Debiopharm, Diaceutics, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Roche Diagnostics/Ventana, Jannsen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Roche Diagnostics/Ventana, Medscape, Prime Oncology; Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Leadership Role, Past Pathology Committee Chair: IASLC; Non-Financial Interests, Member, Lobbying and pressure group for UK - generally writing reports to lobby government.: UK Lung Cancer Consortium. F. Tanaka: Financial Interests, Personal, Research Grant: Boehringer Ingelheim Japan, Ono pharmaceutical, Taiho pharmaceutical, Illy Lilly Japan, Chugai pharmaceutical ; Financial Interests, Personal, Other, consulting fees: AstraZeneca, Chugai Pharmaceuticals, Ono Pharmaceuticals; Financial Interests, Personal, Other, honoraria: MSD, Bristol-Meyers Squibb, Boehringer Ingelheim Japan, Ono pharmaceutical, Johnson & Johnson, Covidien Japan, Taiho pharmaceutical, Illy Lilly Japan, AstraZeneca, Chugai pharmaceutical, Kyowa-Kirin, Takeda pharmaceutical, Pfizer Olympus, Stryker, Intui. M.P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. J.L. Cai: Financial Interests, Personal, Other, Support for attending meetings and/or travel: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. J. Mahmood: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. S. Meadows-Shropshire: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Family member is an employee: AstraZeneca. All other authors have declared no conflicts of interest.