LBA52 - Interim analysis of GALAXIES Lung-201: Phase II, randomized, open-label platform study of belrestotug plus dostarlimab in patients (pts) with previously untreated locally advanced/metastatic (LA/M) PD-L1 high (TPS >/=50%) non-small cell lung cancer (NSCLC)

Background

Less than 50% of pts with unresectable LA/M PD-L1 high NSCLC respond to 1L immunotherapy (IO) necessitating new treatment approaches [1–3]. GALAXIES Lung-201 (NCT05565378) is a Phase 2, open-label, randomized platform study evaluating novel IO combinations including belrestotug (anti-TIGIT) + dostarlimab (anti–PD-1) in previously untreated PD-L1 high LA/M NSCLC.

Methods

Pts with previously untreated, unresectable, PD-L1 high (tumor positive score [TPS] >/=50% confirmed locally or centrally via DAKO 22C3 [local only] or VENTANA SP263) LA/M NSCLC with no actionable mutations were randomized to dostarlimab 500 mg alone or with belrestotug (Substudy 1) at 100 mg (A), 400 mg (B) or 1000 mg (C) every 3 weeks until disease progression, intolerable toxicity or death. The primary endpoint is objective response rate (ORR) per RECIST 1.1 by investigator assessment.

Results

At data cut off (7 June 2024), 32, 30, 32 and 30 pts in dostarlimab, A, B and C were included in this follow up (FU) interim analysis (IA) of preliminary efficacy and safety (modified intent-to-treat population defined as >/=5.6 months FU). Median overall FU was 7.3 months and 65% of pts remain ongoing. A, B and C had greater ORR and a higher incidence of Grade (Gr) 3+ treatment related adverse events (TRAEs), which were considered manageable, vs dostarlimab. Table: LBA52

*Complete or partial response confirmed by repeat imaging >/=4 weeks after response criteria first met CI, confidence interval; TR irAE, treatment related immune related AE

Conclusions

At this IA, belrestotug + dostarlimab demonstrated clinically meaningful anti-tumor activity at each dose and a manageable safety profile, supporting further evaluation in pts with previously untreated, unresectable LA/M PD-L1 high NSCLC. 1. Reck M, et al. J Clin Oncol 2021;39:2339–49 2. Leonetti A. Eur J Cancer 2024;202:114006 3. Guo H, et al. Medicine 2024;103:e36861.

Clinical trial identification

NCT05565378; EudraCT 2021-005115-32.

Editorial acknowledgement

The authors would like to thank January Baron, Lindsey Parker, Lisa Kurz and Nicole Lewis for their contributions. Medical writing support was provided by Aithne Atkinson, PhD, and Elizabeth Ohneck, PhD, of Fishawack Indicia, part of Avalere Health, and funded by GSK.

Legal entity responsible for the study

GSK and iTeos Therapeutics (GSK Study 213824; NCT05565378; EudraCT 2021-005115-32).

Funding

GSK, iTeos Therapuetics.

Disclosure

D.R. Spigel: Financial Interests, Institutional, Research Funding: AbbVie, Agios, Amgen, AnHeart Therapeutics, Apollomics, Arcus, Arrys Therapeutics, Ascendis Pharma, Asher Biotherapeutics, Astellas, AstraZeneca, Bayer, BeiGene, BioNTech RNA Pharmaceuticals, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb; Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GSK, Ipsen Biopharmaceuticals, Jazz Pharmaceuticals, Lyell, MedImmune, ModeX Therapeutics, Novartis, Novocure, Roche/Genentech, Sanofi-Aventis. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co.Ltd; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services Japan K.K, Syneos Health Clinical K.K., EPS Corporation., Nippon Kayaku Co.,Ltd., Takeda Pharmaceutical Co.,Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co.,Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co.,Ltd,., Covance Japan Inc., EP-CRSU CO., LTD., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Caner Research Organization, Ono Pharmaceutical Co.,Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co.,Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. R. Corre: Non-Financial Interests, Personal, Local PI: GSK; Financial Interests, Personal, Expert Testimony: Roche, Sanofi, BMS, MSD, Astra- Zeneca • Financial interests • Non-financial interests • Other • Personal • Institutional • Personal and Institutional • Advisory Board • Advisory Role • Affiliate • Coordinating PI • Expert Testimony • Financially compensated role • Full or part-t. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, Kanaph Therapeutic Inc, Cyrus Therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Founder: DAAN Biotherapeutics; Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd.. A. Psyrri: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, eTheRNA immunotherapies, GSK, LEO, Merck Serono, Merus, -Merus Pharmaceuticals, MSD, Pfizer, Rakuten, Sanofi, Seagen; Financial Interests, Personal, Invited Speaker: EPICS, Merck Serono, MSD; Financial Interests, Personal and Institutional, Funding: Amgen, BI, Demo, Genesis, Kura Oncology, Oncolytics Biotech, Pfizer, Roche; Financial Interests, Personal and Institutional, Local PI: Amgen, AstraZeneca, BI, Debiopharm, GENESIS, GSK, Incyte, Jannsen, Lilly, MSD, Novartis, Oncolytics Biotech, Peregrine, Pfizer, Regeneron, Roche, Sanofi; Non-Financial Interests, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Funding: GSK, Merck Serono, Pfizer; Financial Interests, Personal, Steering Committee Member: GSK, Merus Pharmaceuticals; Financial Interests, Personal and Institutional, Steering Committee Member: Iovance, Pfizer, Roche; Financial Interests, Institutional, Steering Committee Member: Kura Oncology; Non-Financial Interests, Steering Committee Member: Kura Oncology; Financial Interests, Personal and Institutional, Other, Educational activity: Medscape; Financial Interests, Personal, Other, Educational activity: PrimeOncology; Financial Interests, Institutional, Local PI: Replimmune. E. Parkhomenko: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks/Shares: GSK. D. Baxter: Financial Interests, Personal and Institutional, Full or part-time Employment: GSK. N. Patel: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK. F. Trinchese: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK. I. Diaz-Padilla: Financial Interests, Personal, Stocks/Shares: GSK; Financial Interests, Personal, Full or part-time Employment: GSK. M. Reck: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GSK, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche, Seagen; Non-Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GSK, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche, Seagen; Non-Financial Interests, Personal, Other: DMSB: Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Research Funding: Boehringer Ingelheim, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche, Seagen. All other authors have declared no conflicts of interest.