創勝集團 - 全整合型國際化生物制藥公司
創勝集團, 生物藥, 抗體, 藥物研發
05 Jun, 2023
Lin Shen1, Dan Liu1, Ning Li2, Weijian Guo2, Tianshu Liu2, Hongli Li2, Jiayi Li2, Yuxian Bai2, Yanhong Deng2, Zhixiang Zhuang2, Meili Sun2, Qingxia Fan2, Fuyou Zhao2, Liang Han2, Zhenzhong Xia3,
Jianming Wang3, Chuan Qi3, Li Xu3, Xueming Qian3, Caroline Germa3
1. Peking University Cancer Hospital.
3. Transcenta Therapeutics Inc
Adding an anti-claudin18.2(CLDN18.2) antibody to a chemotherapy is a clinically validated approach for patients with high CLDN18.2 expressing gastric tumors.
TST001 is a potential best-in-class antibody with higher CLDN18.2 binding affinity and lower fucose, resulting in enhanced antibody-dependent cellular cytotoxicity (ADCC) activity.
Pre-clinical studies showed that TST001 has stronger tumor growth inhibition effect than the IMAB362-analog at the same dose, regardless of CLDN18.2 expression levels, which may lead to anti-tumor activity even in low to median CLDN18.2-expressing gastric cancer.
As of April 21st, 2023, 64 patients were dosed with TST001 in combination with CAPOX, 15 patients received TST001 at doses ranging from 1 to 8 mg/kg Q3W in the dose escalation and 49 patients at 6 mg/kg in the expansion phase. 41 out of 49 patients in dose expansion were CLDN18.2 positive (defined in method). The median follow up is 197.5 days. Patient characteristics were typical of 1st line G/GEJ cancer, with relatively higher percentage of peritoneal disease (40.6%). 18 patients are still on treatment.
No patients experienced dose-limiting toxicity; Treatment-emergent adverse events (TEAEs) were mostly grade 1-2, including nausea, hypoalbuminaemia, anaemia and vomiting. Only one patient experienced grade 3 nausea and vomiting at dose of 6mg/kg, one patient experienced grade 3 hypoalbuminaemia at dose of 8mg/kg. No patient experienced such event of grade 4.