140P - Prevalence of claudin-18 isoform 2 (CLDN18.2) positivity in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma in patients (pts) in the Asia region: Phase III SPOTLIGHT and GLOW studies

Background

New therapies are needed for pts with LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 is a novel validated target expressed in healthy gastric mucosa, often retained in G/GEJ tumor cells. The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies demonstrated clinically meaningful and statistically significant improvement in progression-free and overall survival with first-line (1L) zolbetuximab (anti-CLDN18.2) + chemotherapy (mFOLFOX6 or CAPOX, respectively) vs placebo + chemotherapy in pts with CLDN18.2+/HER2− disease. We report the biomarker analysis of pts in the Asia region (Japan, Malaysia, South Korea, Taiwan, Thailand).

Methods

Pts with LA unresectable or mG/GEJ adenocarcinoma were screened for CLDN18.2 status by immunohistochemistry (IHC) during screening. Tumors with ≥75% tumor cells with moderate-to-strong membranous CLDN18 staining per the investigational VENTANA CLDN18 (43-14A) RxDx Assay were defined as CLDN18.2+. HER2 status was screened per central/local assessment. Pts in mainland China were excluded.

Results

Across SPOTLIGHT and GLOW, 36.4% (465/1276) of pts in the Asia region with valid CLDN18 IHC results had CLDN18.2+ tumors. The prevalence of CLND18.2 positivity was 46.2% (73/158) in pts from Thailand, 40.2% (41/102) in pts from Malaysia, 39.0% (64/164) in pts from Taiwan, 35.3% (153/434) in pts from Japan, and 32.1% (134/418) in pts from South Korea. The prevalence of CLDN18.2 positivity was 41.0% (178/434) in women and 34.1% (287/842) in men; and 38.4% (296/771) in pts ≤65 years of age and 33.5% (169/505) in pts >65 years of age.

Conclusions

A high CLDN18.2 prevalence rate (36.4%) was observed in the Asia region which was similar to the global prevalence observed in both the SPOTLIGHT and GLOW phase 3 studies. These data support the relevance of CLDN18.2 as a biomarker in Asian pts with LA unresectable or mG/GEJ adenocarcinoma, for whom zolbetuximab + chemotherapy represents a potential 1L therapy.

Clinical trial identification

NCT03504397, 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, of Oxford PharmaGenesis Inc., and was funded by Astellas Pharma Inc.

Legal entity responsible for the study

Astellas Pharma Inc.

Funding

Astellas Pharma Inc.

Disclosure

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. 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., NovaRock Biotherapeutics Limited, Qilu Pharmaceutical. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. Y. Chao: Financial Interests, Personal, Research Grant: Astellas Pharma Global Development, Inc. H.H.F. Soo, P. Sunpaweravong: Financial Interests, Personal, Research Funding: Astellas Pharma Global Development, Inc. D. Moran, A. Guerrero, R. Li, J. Pavese, M. Matsangou, P. Bhattacharya: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Global Development, Inc. K. Shitara: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono, MSD, Taiho, Novartis, AbbVie, GSK, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Guardant Health Japan Corp, Astellas Pharma Inc.; Financial Interests, Institutional, Research Grant: Astellas, Ono, Daiichi Sankyo, Taiho, Chugai, MSD, Eisai, Amgen; Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K. R. Xu: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Henrui, BeiGene, Astellas, Merck, Junshi.