Abstract 340: Development of high affinity anti-CLDN18.2 antibody to treat gastric cancers

Abstract Claudins are tight junction proteins that regulate epithelial-cell barrier function and polarity. Gastric lineage-specific isoform 2 of CLDN18 (CLDN18.2) has been proposed as therapy target in primary/metastatic gastric cancers and CLDN18.2-ectopically-activated cancers, such as pancreatic, esophageal and lung adenocarcinomas. As demonstrated by Zolbetuximab, a monoclonal chimeric antibody directing CLDN18.2, the median overall survival was prolonged to 16.7 months when treated with Zolbetuximab+EOX (OS of EOX group: 9.0 months) in pre-screened CLDN18.2 highly expressing patients (2+/3+ staining in ≥70% tumor cells). Expression of CLDN18.2 in gastric tumors in Chinese population, however, showed diverse levels of frequency with low-frequency expression in a significant portion of tumor cells. Antibody of high affinity is expected to have advantage in targeting antigen of low-frequency, thus clearing tiny lesions clinically. We developed a high affinity anti-CLDN18.2 antibody, GB7004-09. GB7004-09 binded to human/mouse CLDN18.2 while sparing CLDN18.1. It displayed significantly better binding/ADCC/CDC potency against CLDN18.2 expressing tumor cells comparing to leading clinical drug entity. And its in vitro superiority translated to greater in vivo efficacy. Humanization version of GB7004-09, GB7004-09hu15, has been put into preliminary toxicity and PK study. As we are observing safety, stability and activity of GB7004-09hu15, GB7004-09hu15 is a promising agent for extended clinical exploration in cancer indications mention above Citation Format: Zhenhao Zhou. Development of high affinity anti-CLDN18.2 antibody to treat gastric cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 340.