LBA2 - Clinical outcomes with perioperative nivolumab (NIVO) in patients (PTS) with resectable NSCLC from the phase III CheckMate 77T study

Background

In CheckMate 77T, perioperative NIVO demonstrated statistically significant and clinically meaningful EFS benefit vs neoadjuvant (neoadj) chemo followed by adjuvant (adj) placebo (PBO) in pts with resectable NSCLC (HR 0.58, 97.36% CI 0.42–0.81; P = 0.00025). pCR and MPR rates were also improved with perioperative NIVO. Here, we report clinical outcomes by number of neoadj treatment (tx) cycles.

Methods

Adults with untreated, resectable stage IIA–IIIB NSCLC (AJCC 8^th ed) were randomized 1:1 to NIVO 360 mg Q3W + chemo (4 cycles) followed by adj NIVO 480 mg Q4W (1 y) or PBO Q3W + chemo (4 cycles) followed by adj PBO Q4W (1 y). Primary endpoint: EFS. Exploratory analyses: pCR, MPR, EFS, TTDM, and safety by number of completed neoadj tx cycles (< 4 and 4); TTDM in randomized pts (prespecified) and by pathologic response.

Results

Of 461 randomized pts (median f/u 25.4 mo), 191 (83%; NIVO) and 205 (88%; chemo) completed 4 cycles of neoadj tx; the majority of pts who discontinued neoadj tx did so due to study drug toxicity. Baseline characteristics were similar for pts who completed < 4 or 4 cycles of neoadj tx in both tx arms, except that a higher proportion of pts who completed < 4 cycles were from Asia. In pts who completed < 4 cycles of neoadj tx (NIVO, 38; chemo, 27), pCR, MPR, and EFS favored NIVO vs chemo (table); 53% and 37% had surgery, respectively, and among these pts, pCR rates were 35% vs 0% and MPR rates were 40% vs 0%. In pts who completed 4 cycles of neoadj tx, pCR, MPR, and EFS were improved with NIVO vs chemo (table). TTDM favored NIVO vs chemo in all randomized pts (HR 0.62, 95% CI 0.44–0.85) and regardless of number of completed neoadj tx cycles or pCR/MPR status (data to be presented). No new safety signals were seen. Table: 77T

Conclusions

In these exploratory analyses from CheckMate 77T, perioperative NIVO showed clinical benefit in pts with resectable NSCLC, including those who received < 4 cycles of neoadj NIVO + chemo, further supporting perioperative NIVO as a tx option for this pt population.

Clinical trial identification

NCT04025879 (release date: July 17, 2019).

Editorial acknowledgement

Medical writing and editorial support for the development of this abstract, under the direction of the authors, was provided by Christine Billecke, PhD, Adel Chowdhury, PharmD, and Michele Salernitano of Ashfield MedComms, an Inizio company, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

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, Personal, Research Grant, research funding: AstraZeneca, Lilly, Genentech, Bristol-Myers Squibb. T. Cascone: Financial Interests, Personal, Invited Speaker, Speaker Fees/Co-Chair Honorarium: AstraZeneca; Financial Interests, Personal, Invited Speaker, Speaker Fees/Interview Honorarium: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory Board Fees: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Board Fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meeting/Conference as Invited Panelist/Co-Chair: AstraZeneca; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Advisory Board as Invited Member: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Speaker Fee: Clinical Care Options; Financial Interests, Personal, Invited Speaker, Speaker Fees/Invited Panelist Honoraria: IDEOlogy Health; Financial Interests, Personal, Other, Conference Co-Chair Honorarium: IDEOlogy Health; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meetings as Invited Speaker or Conference Co-Chair: IDEOlogy Health; Financial Interests, Personal, Invited Speaker, Speaker Fee/Panelist Honorarium: Medscape; Financial Interests, Personal, Invited Speaker, Speaker Fees/Panelist Honoraria: OncLive; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meeting as Invited Speaker and Panelist: OncLive; Financial Interests, Personal, Invited Speaker, Speaker Fee: Peerview; Financial Interests, Personal, Invited Speaker, Speaker Fee: Physician's Education Resource; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meeting as Invited Speaker: Physician's Education Resource; Financial Interests, Personal, Other, Grant Reviewer Honorarium: Mark Foundation For Cancer Research; Financial Interests, Personal, Advisory Board, Advisory Board Fee: Merck; Financial Interests, Personal, Other, Travel/Food/Beverage for Advisory Board as Invited Member: Merck; Financial Interests, Personal, Advisory Board, Advisory Board Fee: Regeneron; Financial Interests, Personal, Advisory Board, Advisory Board Fees: Pfizer; Financial Interests, Personal, Other, Travel Expenses For Conferences as Invited Speaker: ESMO; Financial Interests, Personal, Other, Speaker Fee and Travel Expenses For Conferences as Invited Speaker: SITC; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses For Conferences as Invited Speaker: IASLC; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses for Meeting as Invited Panelist: AATS; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses for Conference as Invited Speaker: Dava Oncology; Financial Interests, Institutional, Invited Speaker, Institutional Clinical Research Funding: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Institutional Clinical Research Funding: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Institutional Research Grant Funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker, Clinical Research: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, The Leading Edge of Cancer Research Symposium Co-chair and Chair (2021 and 2022)Co-Chair, Data and Biospecimen Access Committee (DBAC), 2022 – present: The University of Texas MD Anderson Cancer Center; Non-Financial Interests, Personal, Leadership Role, Co-Chair, Neoadjuvant Immunotherapy Session, 36th SITC Annual Meeting, 11/2021: SITC; Non-Financial Interests, Personal, Leadership Role, Co-Chair, Texas Lung Cancer Conference 2023, and 2024. Austin, TX 4/2023 and 4/2024.: IDEOlogy Health; Non-Financial Interests, Personal, Leadership Role, Co-Chair, The Future of immunotherapy in Thoracic Oncology, Educational Session, ESMO Immuno-Oncology Congress, Geneva, Switzerland, 12/6/2023: ESMO; Non-Financial Interests, Personal, Leadership Role, Co-Chair, Lung Cancer Summit Post-ESMO Congress 2023, sponsored by AstraZeneca, Madrid, Spain 10/24-10/25/2023: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, Chair, Early-Stage NSCLC Session. IASLC Targeted Therapies of Lung Cancer Meeting (TTLC) 2021, Santa Monica, CA, 2/2021Chair, IASLC 2022 World Conference on Lung Cancer, Neoadjuvant and Adjuvant Treatment of NSCLC Session, Vienna, Austria, 8/2022Chair, IASLC 2022 World Conference on Lung Cancer, Immune Landscape and Molecular Profiling of Lung Cancer Session, Vienna, Austria, 8/2022Chair, IASLC 2023 World Conference on Lung Cancer, Pushing the Boundaries: Adjuvant and Neoadjuvant Approaches in Early-Stage Non-small Cell Lung Cancer, Singapore 9/2023: IASLC; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: AACR; Non-Financial Interests, Personal, Member: SITC; Non-Financial Interests, Personal, Member: IASLC; Other, Personal, Other, Food/Beverage Expenses at Conferences: Genentech; Other, Personal, Other, Food/Beverage Expenses at Conferences: Daiichi Sankyo. J. Spicer: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Protalix Biotherapeutics; Financial Interests, Personal, Advisory Board: Xenetic Biosciences; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Invited Speaker, In kind contribution of investigational drug.: AstraZeneca; Financial Interests, Institutional, Invited Speaker, In kind contribution of investigational drug: BMS; Financial Interests, Institutional, Invited Speaker, Grant to institution for research within my laboratory: CLS Therapeutics; Financial Interests, Institutional, Invited Speaker, Grant to institution for execution of research within my laboratory.: Protalix Biotherapeutics; Financial Interests, Institutional, Invited Speaker, Grant to institution for execution of multi-center clinical trial: Roche; Financial Interests, Institutional, Invited Speaker, Grant to institution for execution of clinical trial: Merck; Non-Financial Interests, Personal, Principal Investigator, Clinical trial chair for IND 242 Neoadjuvant Platform Trial in Patients with Surgically Resectable Non-Small Cell Lung Cancer (NSCLC): Canadian Cancer Trials Group. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh; Financial Interests, Institutional, Invited Speaker: Astra Zeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Hengrui; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: Hutchison MediPharma; Financial Interests, Institutional, Advisory Board: ZaiLab; Financial Interests, Institutional, Advisory Board: GenomiCare; Financial Interests, Institutional, Advisory Board: Yuhan Corporation; Financial Interests, Institutional, Advisory Board: Menarini; Financial Interests, Institutional, Advisory Board: Inventis Bio Co.Ltd; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Hutchison; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Heng Rui; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Hansoh; Financial Interests, Personal, Research Grant: Beigene; Financial Interests, Personal, Research Grant: Lilly Suzhou Pharmaceutical Co.Ltd; Financial Interests, Personal, Invited Speaker: FibroGen. F. Tanaka: Financial Interests, Personal, Research Grant: Boehringer Ingelheim Japan, Ono pharmaceutical, Taiho pharmaceutical, Illy Lilly Japan, Chugai pharmaceutical; Financial Interests, Personal, Other, consultant: AstraZeneca, Chugai Pharmaceuticals, Ono Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: 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. R. Cornelissen: Financial Interests, Personal, Other, consultant: Janssen, MSD, Spectrum. J. Kuzdzal: Financial Interests, Personal, Principal Investigator, PI in clinical studies: BMS, Roche; Financial Interests, Personal, Speaker’s Bureau: the Jagiellonian University Medical College; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Jagiellonian University Medical College ; Financial Interests, Personal, Leadership Role: Regional Govermaent Consultant in Thoracic Surgery; Financial Interests, Personal, Stocks/Shares: Medycyna Praktyczna Publishing House, Medycyna Praktyczna Education, and Technet printing company. L. Wu: Financial Interests, Personal, Speaker’s Bureau: MSD, AstraZeneca, Roche China, Bristol-Myers Squib, Pfizer, Lilly, Innovate Biopharmaceuticals, Hengrui Medicine. J. Pujol: Financial Interests, Personal, Other, funding, provision of study materials: Montpellier Academic Hospital. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics. L.D.O.M. Koch: Financial Interests, Personal, Invited Speaker, Support for attending meetings and/or travel: MSD, BMS. C. Coronado Erdmann: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Incyte. S. Meadows-Shropshire: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Janssen; Non-Financial Interests, Personal, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Personal, Leadership Role, Insutituto Investigación Sanitaria Puerta de Hierro: Director. All other authors have declared no conflicts of interest.