Authors:

Weijian Guo¹, Jifang Gong³, Caroline Germa², Chuan Qi², Chunhua Qian², Jenny Yao², Jianming Wang², Li Xu²,Lijuan Zhang², Xueming Qian², Zhenzhong Xia², Lin Shen³

1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China;

2. Suzhou Transcenta Therapeutics Co., Ltd.,

3.  Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China

Background:

• Gastric cancer (GC) remained the 4th leading cause of cancer death worldwide, accounting for about 7.7% of all cancer related mortality¹.

• Combinations of platinum and fluoropyrimidine are the preferred first-line chemotherapy regimen for patients with HER2 negative advanced gastric cancer². Recently, Nivolumab was approved in combination with chemotherapy for first-line treatment of patients with advanced or metastatic gastric cancer. Though treatment outcome being improved, the median overall survival of nivolumab plus chemotherapy was still less than 14 months³.

• Claudin-18 isoform 2 (CLDN18.2) is a member of the human claudin family of tetraspan membrane proteins that are crucial structural and functional components of tight junctions⁴. Unlike other family members, CLDN18.2 expression is strictly limited to differentiated epithelial cells of gastric mucosa^{4, 5}. Interestingly CLDN18.2 is ectopically expressed at a significant level in multiple tumor types including gastric, esophageal, pancreatic and lung cancers, making it an attractive anti-cancer target5. In G/GEJ cancer, its expression is independent from PD-L1⁶.

Trial Status:

• As of Dec 20, 2022, 7 subjects in Cohort G and 3 in Cohort H have been enrolled. The enrollment is ongoing.