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
10 Mar, 2022
Michael Shi* 1, Ning Li2, Jifang Gong3, Weijian Guo4, Jian Zhang4, Nong Xu5, Miao Zhang3, Changsong Qi3, Zhenzhong Xia6, Yu Shen6, Jianming Wang1, Li Xu1, Chuan Qi6, Xueming Qian6, Lin Shen3
1Global R&D, Transcenta Therapeutics, Princeton, United States, 2Clinical Oncology, Henan Cancer Hospital, Zheng Zhou, 3GI Oncology, Peking University Cancer Hospital, Beijing, 4Medical Oncology, Fudan University Cancer Center, Shanghai, 5Medical Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou, 6Global R&D, Transcenta Holding, Suzhou, China
Objectives: Primary objectives are to evaluate the safety and tolerability, to identify MTD and recommended phase 2 dose (RP2D). Secondary objectives include the assessment of pharmacokinetic parameter, immunogenicity, and preliminary anti-cancer activity.
Methods: This phase I clinical trial enrolls patients with advanced or metastatic solid tumors who progressed on or after standard treatments. In the dose escalation phase, patients without preselection of tumor CLDN18.2 expression were given increasing doses of TST001 intravenously every 3 weeks (Q3W) using a 3+3 design.
Results: As of Sept. 7, 2021, 11 patients had been treated at the dose levels of 3, 6, and 10 mg/kg Q3W. Nine patients were DLT evaluable with no DLT reported and MTD has not been reached. TST001 demonstrated a roughly linear PK profile as both Cmax and AUC increased proportionally across the dose range following the first dose. No drug accumulation was observed in Q3W cohort. 10 mg/kg Q3W was designated as RP2D for further expansion study and three additional patients were enrolled into the expansion phase at the 10 mg/kg Q3W dose. The most common AEs (>20%) included nausea (64%), vomiting (50%), anemia (43%), hypoalbuminemia (29%), abdominal distension (21%), constipation (21%). 5 patients experienced Grade 3 AEs, including blood pressure increased, bilirubin conjugated increased, hyponatremia, nausea and vomiting, pulmonary embolism. Two patients experienced 3 SAEs including hypoalbuminemia, jaundice cholestatic; pulmonary embolism. No treatment related Grade 4 or 5 event was reported. One patient with CLDN18.2 overexpression gastric signet ring cell carcinoma who progressed on multiple lines of chemotherapies, anti-PD1 and anti-VEGF therapies in the 6 mg/kg cohort achieved a confirmed partial response at week 12.
Conclusions: TST001 demonstrated a manageable & tolerable safety profile in patients with advanced solid tumors and preliminary anti-tumor activity in a heavily pretreated gastric cancer patient expressing CLDN18.2.