Background

First-line immunotherapy-based regimens have limited efficacy in pts with mNSCLC and tumor PD-L1 < 1%. A high unmet medical need remains in mNSCLC, particularly in pts with squamous (SQ) mNSCLC or baseline brain metastasis (BM). In CheckMate 9LA (NCT03215706), 1L NIVO + IPI + 2 cycles of chemo showed long-term, durable benefit vs chemo in pts with mNSCLC, regardless of tumor PD-L1 status. Here we report an exploratory analysis of efficacy and safety in pts with tumor PD-L1 < 1% by histology or the presence of BM.

Methods

Adults with stage IV/recurrent NSCLC, ECOG PS ≤ 1, and no sensitizing EGFR/ALK alterations were randomized 1:1 to 1L NIVO (360 mg Q3W) + IPI (1 mg/kg Q6W) + chemo (Q3W, 2 cycles) or chemo alone (Q3W, 4 cycles). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were assessed in pts with tumor PD-L1 < 1% by histology (non-SQ [NSQ] or SQ) or by the presence of baseline BM (by blinded independent central review).

Results

Baseline characteristics in pts with tumor PD-L1 < 1% were generally similar to the ITT population. With a minimum follow-up of 36.1 mo (database lock: Feb 15, 2022), survival and efficacy outcomes were improved with NIVO + IPI + chemo vs chemo alone in pts with PD-L1 < 1% and NSQ or SQ histology (Table). Similarly, OS was improved with NIVO + IPI + chemo vs chemo in pts with (n = 17 vs 15) or without (n = 118 vs 114) BM; median OS was 20.6 vs 6.9 mo (HR 0.28, 95% CI 0.13–0.61) and 16.4 vs 11.2 mo (HR 0.72, 95% CI 0.54–0.96), respectively. No new safety signals were observed. Table: 1049P

1049P Efficacy outcomes in pts with tumor PD-L1 < 1% by histology

Conclusions

First-line NIVO + IPI + chemo showed long-term, durable clinical benefit in pts with mNSCLC and tumor PD-L1 < 1% regardless of histology or the presence of baseline BM. These exploratory results were consistent with previous reports from all randomized pts and further support NIVO + IPI + chemo as a 1L treatment option for pts with mNSCLC.

Clinical trial identification

NCT03215706.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Sabrina Hom, PhD, Wendy Sacks, PhD, and Michele Salernitano of Ashfield MedComms, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

T. John: Financial Interests, Personal, Invited Speaker, Speaker tour Vietnam: AstraZeneca; Financial Interests, Personal, Invited Speaker, CTIO: Merck Sharp Dohme; Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Bayer, Specialised Therapeutics; Financial Interests, Institutional, Advisory Board: Roche, Novartis, Pfizer, Amgen, Takeda, PharmaMar. T. Ciuleanu: Financial Interests, Personal, Other, speaker, consultancy, advisory role: Roche, BMS, MSD, Pfizer, Eli Lilly, AstraZeneca, Sanofi, Sandoz, Novartis, Janssen, Astellas, Amgen. M. Schenker: Financial Interests, Personal and Institutional, Invited Speaker, Payment for Clinical trials activities: B.M.S., M.S.D., Roche, Merck Serono, Sanofi, Regeneron, AstraZeneca, Pfizer, G.S.K, Novartis, Astellas, Pharma Mar, BeiGene, Clovis Pharmaceutical, AbbVie, Bioven, Mylan, Samsung Pharmaceutical, Eisai, Gilead, Amgen, Daiichi Sankyo. J. Menezes: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. E.A. Richardet: Financial Interests, Personal, Advisory Board, Speaker Advisory Board: BMS, Pfizer, Boehringer, Astra, Roche, Novartis, Lilly Pharmacia; Financial Interests, Institutional, Research Grant, Research fundings: AstraZeneca BMS, Pfizer, Boehringer, Amgen, Bayer. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc; Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer); Non-Financial Interests, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). O.J. Juan Vidal: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Institutional, Funding: AstraZeneca. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag International NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President, ASEICA (Spanish Association of Cancer Research ); Financial Interests, Other, Foundation President: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche; Financial Interests, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui BeiGene, Roche, Hansoh. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Roche. X. Zhang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D.J. Grootendorst: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. L. Eccles: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D.P. Carbone: Financial Interests, Personal, Other, speaker, consultancy, advisory role: AbbVie, AstraZeneca, G1 Therapeutics, PPD Development, Caris Life Sciences, Curio Science, Genentech, GSK, Iovance Biotherapies, Jazz, Merck, Merck/EMD Serono, Merck KGaA, Mirati, Novartis, Regeneron, Sanofi, Intellisphere, InThought, OncLive, Pfizer. All other authors have declared no conflicts of interest.