LBA1 - CheckMate 77T: Phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC

Background

Neoadjuvant (neoadj) NIVO + chemo provides efficacy benefit vs chemo in patients (pts) with resectable NSCLC. However, the efficacy of perioperative NIVO + chemo has not been evaluated in phase 3 studies. Here, we report prespecified interim analysis results from CheckMate 77T, a randomized, double-blind, phase 3 study evaluating neoadj NIVO + chemo followed by surgery and adjuvant (adj) NIVO (NIVO + chemo/NIVO) compared with neoadj placebo + chemo followed by surgery and adj placebo (chemo/PBO) in resectable stage II–IIIB NSCLC.

Methods

Adults with untreated resectable stage IIA (>4 cm)–IIIB (N2) NSCLC (AJCC v8), EGFR/ALK wild-type, and ECOG PS ≤1 were stratified by tumor histology, PD-L1 expression, and disease stage, and randomized 1:1 to NIVO 360 mg Q3W + platinum-doublet chemo (4 cycles) followed by surgery and adj NIVO 480 mg Q4W (1 y), or placebo Q3W + platinum-doublet chemo (4 cycles) followed by surgery and adj placebo Q4W (1 y). Primary endpoint was EFS (RECIST v1.1 per BICR). Secondary endpoints were pCR and MPR (both per BIPR), OS, and safety.

Results

Baseline characteristics were balanced between arms (NIVO + chemo/NIVO, n = 229; chemo/PBO, n = 232). At a minimum follow-up of 15.7 mo, NIVO + chemo/NIVO significantly improved EFS vs chemo/PBO (median [95% CI], not reached [28.9 mo–not reached] vs 18.4 mo [13.6–28.1]; HR [97.36% CI], 0.58 [0.42–0.81]; P = 0.00025). NIVO + chemo/NIVO also improved pCR rates (25.3% vs 4.7%; odds ratio, 6.64 [95% CI, 3.40–12.97]) and MPR rates (35.4% vs 12.1%; odds ratio: 4.01 [2.48–6.49]) vs chemo/PBO. Definitive surgery rates were 78% vs 77% in the NIVO + chemo/NIVO vs chemo/PBO arms; of these, 89% vs 90% were R0 resections, respectively. Grade 3–4 treatment-related AEs were 32% and 25% in the NIVO + chemo/NIVO and chemo/PBO arms; surgery-related AEs were 12% and 12%, respectively.

Conclusions

CheckMate 77T met its primary endpoint with a statistically significant and clinically meaningful improvement in EFS with neoadj NIVO + chemo followed by surgery and adj NIVO vs chemo/PBO in pts with resectable NSCLC. No new safety signals were noted with the NIVO + chemo/NIVO regimen.

Clinical trial identification

NCT04025879.

Editorial acknowledgement

Editorial assistance was provided by Adel Chowdhury, PharmD and Samantha Dwyer, PhD of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

T. Cascone: Financial Interests, Institutional, Speaker, Consultant, Advisor: Society for Immunotherapy of Cancer (SITC), MarkFoundation for Cancer Research, Bristol Myers Squibb, Roche, Medscape, IDEOlogy Health, Physicians' Education Resource® LLC (PER®), OncLive and PeerView; Financial Interests, Institutional, Advisory Board: MedImmune/AstraZeneca, Bristol Myers Squibb, Merck, Genentech, Arrowhead Pharmaceuticals, Pfizer Inc. and Regeneron; Financial Interests, Institutional, Other, travel and/or food/beverage: SITC, International Association for the Study of Lung Cancer, Parker Institute for Cancer Immunotherapy, Physicians' Education Resource® LLC (PER®), Dava Oncology, IDEOlogy Health, OncLive, MedImmune/AstraZeneca and Bristol Myers Squibb; Financial Interests, Institutional, Research Funding: EMD Serono, MedImmune/AstraZeneca and Bristol Myers Squibb. M.M. Awad: Financial Interests, Personal, Other, consultant: 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. J.D. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, CLS Therapeutics, Protalix Biotherapeutics, Merck, Roche; Financial Interests, Personal, Other, consulting fees: Roche, Merck, BMS, AstraZeneca, Regeneron, Protalix Biotherapeutics, Xenetic Biosciences, Amgen, Novartis; Financial Interests, Personal, Speaker’s Bureau: PeerView, BMS, AstraZeneca Payments to me; Non-Financial Interests, Personal, Advisory Board: PUCC trial; Non-Financial Interests, Personal, Leadership Role: Industry chair for Canadian Association of Thoracic Surgeons. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AdtraZeneca, Prizer, Boehringerlngelheim, 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. B. Sepesi: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting and speaking fees: AstraZeneca, Medscape; Financial Interests, Personal, Speaker, Consultant, Advisor, Speaking fees: PEER VIEW. F. Tanaka: Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim Japan, Ono Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan, Chugai Pharmaceutical; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: MSD, BMS, Boehringer Ingelheim Japan, Ono Pharmaceutical, Johnson and Johnson, Covidien Japan, Taiho Pharmaceutical, Eli Lilly Japan, AstraZeneca, Chugai Pharmaceutical, Kyowa-Kirin, Takeda Pharmaceutical, Pfizer, Olympus, Stryker, Intuitive Japan. J.M. Taube: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: Bristol Myers Squibb, Merck & Co, AstraZeneca, Roche Pharmceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Patent: Machine learning algorithm for irPRC. R. Cornelissen: Financial Interests, Personal, Other, consulting fees: Janssen, MSD, Spectrum; Financial Interests, Personal, Speaker’s Bureau: Librerium; Financial Interests, Personal, Other, Support for attending meetings and travel: Librerium. J. Kuzdzal: Financial Interests, Institutional, Research Funding: BMS, Roche; Financial Interests, Institutional, Research Grant: Jagiellonian University Medical College; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Jagiellonian University Medical College, John Paul II Hospital,; Financial Interests, Personal, Stocks/Shares: Medycyna Praktyczna Publishing House, Medycyna Praktyczna Education, and Technet. L. Wu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS, Hengrui Medicine, Innovate Biopharmaceuticals, Lilly, MSD, Pfizer, Roche. C. Coronado Erdmann: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks or ownership: BMS, Incyte. S. Meadows-Shropshire: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: 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.