Meeting
2022 ASCO Gastrointestinal Cancers Symposium
Zolbetuximab + CAPOX versus CAPOX in first-line treatment of claudin18.2+/HER2–advanced/metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW phase 3 study.
Authors
Manish A. Shah
Weill Cornell Medical College, New York, NY
Manish A. Shah , Jaffer A. Ajani , Salah-Eddin Al-Batran , Yung-Jue Bang , Daniel V.T. Catenacci , Peter C. Enzinger , David H. Ilson , Sunnie S. Kim , Florian Lordick , Kohei Shitara , Eric Van Cutsem , Ahsan Arozullah , Jeffrey J. Raizer , Jung Wook Park , Rui-hua Xu
Organizations
Weill Cornell Medical College, New York, NY, The University of Texas MD Anderson Cancer Center, Houston, TX, University Cancer Center Frankfurt, Institut für Klinisch-Onkologische Forschung am Krankenhaus Nordwest, Frankfurt, Germany, Seoul National University College of Medicine, Seoul, South Korea, Gastrointestinal Oncology Program, University of Chicago, Chicago, IL, Center for Esophageal and Gastric Cancer, Dana-Farber Cancer Institute, Boston, MA, Memorial Sloan Kettering Cancer Center, New York, NY, University of Colorado Comprehensive Cancer Center, Aurora, CO, University Cancer Center Leipzig, Leipzig, Germany, National Cancer Center Hospital East, Kashiwa, Japan, University of Leuven (KUL) and University Hospitals Gasthuisberg, Leuven, Belgium, Astellas Pharma Global Development, Inc., Northbrook, IL, Astellas Pharma Global Development, Inc, Northbrook, IL, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Research Funding
Pharmaceutical/Biotech Company
Background: Despite standard treatment options (eg, CAPOX, capecitabine + oxaliplatin), 5-year survival with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ) is poor and limited biomarkers exist to inform treatment selection. Claudin 18.2 (CLDN18.2), a targetable biomarker, is a tight junction protein that is normally confined to gastric mucosa of healthy tissue and is often retained in G/GEJ. Zolbetuximab, a chimeric IgG1 monoclonal antibody, binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Phase 2 (FAST; Sahin, Ann Oncol. 2021) results showed prolonged survival with zolbetuximab + EOX (epirubicin, oxaliplatin, capecitabine) vs EOX in CLDN18.2+ advanced G/GEJ. Preliminary phase 2 (NCT03505320, ILUSTRO Cohort 2; Klempner, J Clin Oncol. 2021) results showed promising antitumor activity with combination zolbetuximab + mFOLFOX6 (5-fluorouracil, folinic acid, oxaliplatin) in CLDN18.2+ advanced G/GEJ. Methods: GLOW (NCT03653507) is enrolling ̃500 adults from global sites. Patients are required to have radiologically evaluable (RECIST v1.1) CLDN18.2+/HER2– locally advanced unresectable or metastatic G/GEJ. Prior chemotherapy for advanced/metastatic G/GEJ is not permitted. Patients will be randomized 1:1 to zolbetuximab + CAPOX or placebo + CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at 800 mg/m2 IV on Cycle 1 Day 1 (loading dose), then at 600 mg/m2 IV every 3 weeks; 8 cycles of CAPOX will be administered. Central testing of tumor tissue will determine CLDN18.2 status; tumors will be considered CLDN18.2+if ≥75% of tumor cells show moderate to strong membranous immunohistochemical staining. Primary endpoint: progression-free survival per independent review. Secondary endpoints: overall survival; objective response rate; duration of response; safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of September 22, 2021, 135 sites were open for screening and enrollment. Clinical trial information: NCT03653507.
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Abstract Details
Session Type
Trials in Progress Poster Session
Session Title
Trials in Progress Poster Session A: Cancers of the Esophagus and Stomach and Other GI Cancers
Track
Esophageal and Gastric Cancer,Other GI Cancer
Sub Track
Therapeutics
Clinical Trial Registration Number
NCT03653507
DOI
10.1200/JCO.2022.40.4_suppl.TPS365
Abstract #
TPS365
Poster Bd #
M3
Abstract Disclosures
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