1261O - Neoadjuvant nivolumab (N) + ipilimumab (I) vs chemotherapy (C) in the phase III CheckMate 816 trial

Background

The phase 3 CheckMate 816 trial met both of its primary endpoints, with neoadjuvant N + C demonstrating statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathological complete response (pCR) vs C in patients (pts) with resectable NSCLC; N + C continues to show long-term EFS benefit vs C. Here, we report exploratory analyses from the concurrently randomized N + I and C arms of the study.

Methods

Adults with stage IB (≥ 4 cm)–IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK mutations were concurrently randomized to 3 cycles of N 3 mg/kg Q2W + 1 cycle of I 1 mg/kg or 3 cycles of C Q3W. Enrollment to the N + I arm closed early after the primary analysis population of the study was changed to N + C vs C on the basis of evolving external trial data. Assessments included EFS and pCR (per blinded independent review), overall survival (OS), surgical outcomes, safety, and efficacy by a 4-gene (CD8A, STAT1, LAG3, and CD274 [PD-L1]) inflammatory signature score derived from the RNA sequencing of baseline (BL) tumor samples.

Results

In the concurrently randomized N + I (n = 113) and C (n = 108) arms, BL characteristics were generally balanced between treatment (tx) arms. At a median follow-up of 49.2 mo (database lock, 14 Oct 2022), both EFS and OS appeared to favor N + I vs C. Median EFS was 54.8 mo vs 20.9 mo with N + I vs C (HR 0.77 [95% CI 0.51–1.15]; 3-y EFS rates, 56% vs 44%). Median OS was not reached in either tx arm (HR 0.73 [95% CI 0.47–1.14]; 3-y OS rates, 73% vs 61%). pCR rate (95% CI) was higher with N + I vs C (20% [13.4–29.0] vs 5% [1.5–10.5]). Definitive surgery occurred for 74% and 76% of pts in the N + I and C arms, respectively; R0 resection rates were 80% and 71%. A high vs low BL 4-gene inflammatory score was associated with improved EFS and pCR with N + I. Grade 3–4 tx-related adverse events (AEs) and grade 3–4 surgery-related AEs were reported in 14% vs 36% and 15% vs 14% of pts in the N + I and C arms, respectively. Outcomes in key subgroups, including by PD-L1 expression, will be presented.

Conclusions

These exploratory analyses from CheckMate 816 showed potential clinical benefit and a manageable safety profile with neoadjuvant N + I vs C; N + C remains the standard neoadjuvant treatment for pts with resectable NSCLC, as previously reported.

Clinical trial identification

NCT02998528.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Christine Billecke, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

M.M. Awad: Financial Interests, Personal, Speaker, Consultant, Advisor: 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. P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Daiichi, F-Star, G1, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface.; Financial Interests, Institutional, 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; Non-Financial Interests, Personal, Advisory Board: LUNGevity. 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. J.D. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, CLS Therapeutics, Protalix Biotherapeutics, Merck, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Merck, BMS, AstraZeneca, Regeneron, Protalix Biotherapeutics, Xenetic Biosciences, Amgen, Novartis; Financial Interests, Personal, Financially compensated role: PeerView, BMS, AstraZeneca; Non-Financial Interests, Personal, Advisory Board: PUCC trial, Industry chair for Canadian Association of Thoracic Surgeons. C. Wang: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Leadership Role, Vice Chairmen of Oncology committee - National Health Commission Capacity Building and Continuing Education: Vice Chairmen of CSCO-Lung. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AstraZeneca, Pfizer, Boehringer lngelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co.Ltd, Roche, Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co. Ltd; Financial Interests, Coordinating PI: FibroGen. 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: AstraZeneca, 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. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, 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., GSK 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, Speaker’s Bureau: Ethicon. J.R. Brahmer: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, AstraZeneca, Merck, Regeneron; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Johnson and Johnson, Sanofi, GSK, LUNGevity Lung Cancer Research Foundation, Lung Cancer Foundation of America Scientific Advisory Board Member; Financial Interests, Personal, Member of Board of Directors: Society for the Immunotherapy of Cancer (SITC) Board Member. 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; 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. J.L. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb. M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Lilly, Roche, Takeda, Janssen; Non-Financial Interests, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Leadership Role, Insutituto Investigación Sanitaria Puerta de Hierro: Director. All other authors have declared no conflicts of interest.