134MO - Updated efficacy and safety results from phase III GLOW study evaluating zolbetuximab + CAPOX as first-line (1L) treatment for patients with claudin-18 isoform 2-positive (CLDN18.2+), HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma

Background

The phase 3 GLOW study showed statistically significant improvement with 1L zolbetuximab + capecitabine + oxaliplatin (CAPOX) vs placebo (PBO) + CAPOX in PFS (final; median 8.2 vs 6.8 mo, HR 0.69 [95% CI 0.54, 0.87], P = 0.0007) and OS (interim; median 14.4 vs 12.2 mo, HR 0.77 [95% CI 0.62, 0.97], P = 0.0118) in pts with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. We present an updated efficacy and safety analysis with 8.7 mo additional follow-up from the primary analysis.

Methods

Pts were randomly assigned 1:1 to zolbetuximab IV 800 mg/m² (cycle 1, day [D] 1) followed by 600 mg/m² (every 3 weeks) + CAPOX (oral capecitabine BID on D1–14 and oxaliplatin IV on D1) for eight 21-day cycles or to PBO + CAPOX; pts without progressive disease (PD) continued beyond cycle 8 with zolbetuximab or PBO, + capecitabine at investigator’s discretion, until PD or discontinuation criteria were met. Primary endpoint was PFS per RECIST v1.1 by IRC; OS was a key secondary endpoint.

Results

At data cutoff (June 29, 2023), 507 pts were assigned to zolbetuximab + CAPOX (n = 254) or PBO + CAPOX (n = 253). In zolbetuximab vs PBO arms, median follow-up was 17.8 vs 15.1 mo for PFS and 26.1 vs 26.2 mo for OS, respectively. Median PFS in zolbetuximab vs PBO arms was 8.3 vs 6.8 mo (HR 0.68 [95% CI 0.55, 0.85], P = 0.0004). Median OS in zolbetuximab vs PBO arms was 14.3 vs 12.2 mo (HR 0.77 [95% CI 0.62, 0.95], P = 0.0079); 24-mo OS rate was 28.3% vs 18.8%, with follow-up ongoing through final analyses. Most common TEAEs with zolbetuximab + CAPOX were nausea (zolbetuximab arm: 68.9% vs PBO arm: 50.2%), vomiting (66.1% vs 31.3%), and decreased appetite (41.3% vs 34.5%); incidences of serious TEAEs were similar between arms (48.0% vs 50.6%).

Conclusions

Zolbetuximab + CAPOX continued to demonstrate statistically significant improvement in PFS and OS compared with PBO + CAPOX, with no new safety signals, supporting zolbetuximab + CAPOX as a potential new option for 1L treatment of patients with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma.

Clinical trial identification

NCT03653507.

Editorial acknowledgement

Medical writing support, conducted in accordance with Good Publication Practice (GPP 2022) and the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Ann Ferguson, PhD, and Jing Xu, PhD, of Oxford PharmaGenesis Inc.

Legal entity responsible for the study

Astellas Pharma Inc.

Funding

Astellas Pharma Inc.

Disclosure

F. Lordick: Financial Interests, Personal, Advisory Board: Amgen, Astellas, BMS, Bayer, BeiGene, Biontech, Eli Lilly, Elsevier, MSD, Novartis, Roche, Daiichi Sankyo, PAGE; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eli Lilly, Imedex, Incyte, MSD, MedUpdate, Medscape, Merck Serono, Roche, Servier, StreamedUp!, Daiichi Sankyo, Novartis, Art Tempi; Financial Interests, Personal, Writing Engagement: Deutscher Ärzteverlag, Iomedico, Springer-Nature; Financial Interests, Institutional, Research Grant: BMS, Gilead. M.A. Shah: Financial Interests, Personal, Research Funding: Astellas Pharma Inc., Merck, Bristol Myers Squibb, and Oncolys BioPharma; Financial Interests, Personal, Leadership Role: ASCO Leadership Council. K. Shitara: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, AbbVie, GSK, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Guardant Health Japan Corp, Astellas Pharma Inc.; Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai, MSD, Eisai, Amgen. J.A. Ajani: Financial Interests, Personal, Research Funding: Astellas Pharma Inc., Turning Point Therapeutics, Inc., Bristol Myers Squibb, Merck, Taiho Pharmaceutical, Delta-Fly Pharma, Inc., Roche, ProLynx Inc, Zymeworks, Daiichi Sankyo, Leap Therapeutics, Inc., Gilead Sciences, Inc., and Lanova Pharma; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck, Astellas Pharma Inc., Amgen, Taiho Pharmaceutical, Zymeworks, BeiGene, AstraZeneca, Daiichi Sankyo, Bayer, GRAIL, Novartis, Geneos, Servier Laboratories, and Gilead Sciences, Inc.; Financial Interests, Personal, Other, travel: Daiichi Sankyo, Bristol Myers Squibb, and Merck. Y. Bang: Financial Interests, Personal, Research Funding: Astellas Pharma Inc., Genentech, Roche, Merck Serono, Daiichi Sankyo, MSD, Amgen, and BeiGene; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Daiichi Sankyo, ALX Oncology, Hanmi Pharmaceutical, Merck Serono, Astellas Pharma Inc., Samyang Biopharm Corporation, and Daewoong Pharmaceutical. P.C. Enzinger: Financial Interests, Personal, Research Funding: Astellas Pharma Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: ALX Oncology, Arcus Biosciences, Astellas Pharma Inc., AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Chimeric Therapeutics, Celgene, Coherus BioSciences, Daiichi Sankyo, Five Prime Therapeutics, Inc., IDEAYA Biosciences, Istari Oncology, Legend. D.H. Ilson: Financial Interests, Personal, Research Funding: Astellas Pharma Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Bayer, Astellas Pharma Inc., Merck, Daiichi Sankyo, Taiho Pharmaceutical, Natera Inc, Bristol Myers Squibb, Eli Lilly and Company, Roche, and AstraZeneca; Financial Interests, Personal, Advisory Board: MacroGenics, and Merck. E. van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. J. Gallego Plazas: Financial Interests, Personal, Advisory Board: AAA, Amgen, Bayer, BMS, Eisai, Ipsen, Lilly, Merck, MSD, Pierre Fabre, Roche, Servier; Financial Interests, Personal, Invited Speaker: AAA, Amgen, Bayer, BMS, Ipsen, Lilly, Merck, MSD, Novartis, Servier; Financial Interests, Personal, Other, Educational: Amgen, Ipsen, Merck, Novartis, Pierre Fabre, Roche; Financial Interests, Institutional, Funding: Astellas, AstraZeneca, BMS, Daiichi Sankyo, Lilly, Servier; Non-Financial Interests, Personal, Member of Board of Directors: Spanish Society Medical Oncology, Spanish Group of Neuroendocrine an Endocrine Tumours; Non-Financial Interests, Personal, Project Lead: AGAMENON-SEOM Registry of Esophagohastric Cancer. J. Huang: Financial Interests, Personal, Research Funding: Astellas Pharma Inc. L. Shen: Financial Interests, Personal, Other, Consulting fees: Mingji biopharmaceutical, Haichuang pharmaceutical, Herbour biomed; Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, BI, Sanofi, Roche, Servier, AZ; Financial Interests, Institutional, Funding: Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical (Shanghai), Alphamab Oncology, Yaojie Ankang (Nanjing) Technology Co., Ltd., BeiGene, Ltd., Qiyu Biotechnology (Shanghai) Co., Ltd., BriSTAR immunotech; Financial Interests, Institutional, Local PI: Merck Healthcare KGaA, Roche; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Innovent, BeiGene, Ltd., Qilu Pharmaceutical, NovaRock Biotherapeutics Limited. S.C. Oh, H.H.F. Soo, H.M. Türk, J.W. Park, D. Moran, P. Bhattacharya: Financial Interests, Personal, Research Funding: Astellas Pharma Inc. Y.J. Cao: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Global Development, Inc. R. Xu: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Henrui, BeiGene, Astellas, Merck, Junshi.