7MO: A phase II trial of tobemstomig (tobe) + platinum-based chemotherapy (chemo) vs pembrolizumab (pembro) + chemo in patients (pts) with untreated locally advanced or metastatic non-small cell lung cancer (NSCLC).

Abstract

Background Tobemstomig (tobe) is a novel bispecific antibody targeting programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3). BO44178 (NCT05775289) is a randomised, double-blind, phase II study evaluating tobe + chemo vs pembro + chemo in pts with NSCLC who are ineligible for surgery or definitive chemoradiotherapy. Methods Eligible pts with previously untreated, locally advanced unresectable or metastatic NSCLC were randomised 1:1 to receive either induction tobe + chemo (carboplatin + paclitaxel/pemetrexed) or pembro + chemo for four 21-day cycles, followed by maintenance tobe or pembro with/without pemetrexed every 3 weeks until disease progression, toxicity or loss of clinical benefit. Pts were stratified by PD-ligand 1 expression, histology and smoking status. Primary endpoints: confirmed objective response rate (ORR); progression-free survival (PFS). Secondary endpoints included overall survival (OS), duration of response (DoR) and safety. Results At data cutoff (20 June 2024), 181 pts were randomised to receive tobe + chemo (n = 90) or pembro + chemo (n = 91). Median duration of follow-up was 6 months. Baseline characteristics were similar across treatment arms; median age was 66 years. There was no improvement in confirmed ORR with tobe + chemo (41.1%) vs pembro + chemo (46.2%) and no PFS difference was observed between treatment arms (HR 0.99; 95% CI 0.63, 1.56; Table). OS data were immature at this analysis. Efficacy results were consistent across subgroups. The rates of grade 3/4 adverse events (AEs), serious AEs and immune-mediated AEs were higher with tobe + chemo vs pembro + chemo; however, the rate of treatment withdrawal due to AEs was similar between arms. [Formula presented] Conclusions At this interim analysis, no ORR or PFS benefit was observed in pts with untreated locally advanced or metastatic NSCLC receiving tobe + chemo over pembro + chemo. OS data remain immature. Clinical trial identification NCT05775289. Editorial acknowledgement This study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance was provided by Vanessa Poon, MRes, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd. Legal entity responsible for the study F. Hoffmann-La Roche Ltd. Funding F. Hoffmann-La Roche Ltd. Disclosure E. Nadal: Financial Interests, Personal, Advisory Board: Amgen, Apollomics, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Genmab, Janssen, Lilly, Merck Sharp Dohme, Pfizer, Pierre Fabre, Qiagen, Regeneron, Roche, Sanofi, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Illumina, Janssen, Lilly, Merck Serono, Merck Sharp Dohme, Pfizer, Qiagen, Roche, Sanofi, Takeda; Non-Financial Interests, Personal and Institutional, Funding, Funding for a clinical trial: Bristol Myers Squibb, Merck Serono, Roche; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Transgene; Other, Personal, Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). A. Rittmeyer: Financial Interests, Personal, Speaker's Bureau: BMS, Roche, MSD, Lilly; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim. Daichi Sankyo, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche. F. de Marinis: Financial Interests, Personal, Invited Speaker: Roche, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche- Genentech, DaiichiBMS, Novartis, Takeda, Eli Lilly, Mirati, Merck, MSD, Regeneron, Xcovery; Non-Financial Interests, Personal, Principal Investigator, IEO: AbbVie, Ariad, AstraZeneca, Blue Medicine, GSK, Incyte, Mirati, Takeda, Novartis, MSD, Sanofi, PharmaMar, Takeda. D.H. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, ChongKeunDang, Janssen, MSD, Novartis, Ono, Pfizer, Roche, ST Cube, AbbVie, and Abion; Financial Interests, Personal, Advisory Board: ST Cube and Abion; Financial Interests, Personal, Member of Board of Directors: ST Cube. S. Gadgeel: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech/Roche, Boehringer-Ingelheim, AbbVie, Astellas, Bristol Myers Squibb, Pfizer, Amgen, Johnson and Johnson, Daiichi, Gilead; Financial Interests, Institutional, Principal Investigator: Tango, AstraZeneca, Pfizer, Amgen, Novita, Kymera, Bayer, Genentech/Roche, Bristol Myers Squibb, D3Bio, Debio Pharma, Daiichi Sankyo Gilead, Janux Therapeutics, Arrivent, Genmab, GRAIL, IOVANCE, JAB Therapeutics, AbbVie, Monte Rosa, Nuvalent, Regeneron. E. Bria: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Roche, Pfizer, Takeda, Eli-Lilly, BMS, Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Pfizer, Takeda, Eli-Lilly, BMS, Novartis, Celltrion, Daiichi Sankyo, Johnson & Johnson; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. S. Arulananda: Financial Interests, Personal, Invited Speaker: Merck-Sharpe & Dohme, AstraZeneca, Roche, Bristol Myers Squibb, Merck Serono, Takeda, Medwise consulting, Amgen; Financial Interests, Personal, Advisory Board: Roche, BeiGene, Amgen, Bayer, AstraZeneca, Merck-Sharpe & Dohme, Johnson & Johnson, Bristol Myers Squibb, Medison. E.H. Cronenberg: Financial Interests, Institutional, Principal Investigator: Roche. V. Antic: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. E. Bennett: Financial Interests, Institutional, Full or part-time Employment: F. Hoffmann-La Roche/Genentech; Financial Interests, Institutional, Stocks/Shares: F. Hoffmann-La Roche/Genentech. Y. Hu: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche AG; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche AG. K. Madden-Raja: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. P. Williams: Financial Interests, Institutional, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Institutional, Leadership Role: Genentech. H. Prizant: Financial Interests, Institutional, Full or part-time Employment: Genentech/Roche; Financial Interests, Institutional, Stocks/Shares: Genentech/Roche. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Guardant Health, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx, AnHeart, Arcus Biosciences, Ellipses, Gilead, IO Biotech, Mirati; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Novocure, PharmaMar; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Invited Speaker: Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Personal, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role, Mesothelioma Committee, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Personal, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Personal, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Personal, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. All other authors have declared no conflicts of interest.Copyright © 2025 International Association for the Study of Lung Cancer, Published by Elsevier Ltd