First-in-human dose escalation and expansion study of SYSA1801, an antibody-drug conjugate targeting claudin 18.2 in patients with resistant/refractory solid tumors.

作者：Yakun Wang, Jifang Gong, Rongbo Lin, Shen Zhao, Jufeng Wang, Qianli Wang, Yanqiao Zhang, Dan Su, Jingdong Zhang, Qian Dong, Ling Lin, Wen Tian, Ying Chen, Yang Yang, Xueyuan Zhang, Xuechao Wan, Jinfeng Gao, Na An, Valerie M. Jansen, Lin Shen · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.3016 · 被引用次数：32 · 研究领域：Barrier Structure and Function Studies、Ferroptosis and cancer prognosis、Radiomics and Machine Learning in Medical Imaging

3016 Background: SYSA1801 is a MMAE antibody-drug conjugate (ADC) targeting claudin 18.2 (CLDN18.2), a tight junction protein broadly expressed in gastric, pancreatic, and other solid tumors. CLDN18.2 has a highly selective cell surface expression profile that is limited to normal gastric mucosa, making it a promising ADC therapeutic target. SYSA1801 has shown significant in vitro and in vivo anti-tumor activity in multiple cell lines and patient-derived xenografts expressing CLDN18.2. Methods: This is an open-label, multi-center, phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy of SYSA1801 in patients (pts) with histologically confirmed resistant/refractory solid tumors that express CLDN18.2 who progressed on or were intolerant to standard treatment, or had no standard treatment. This study consists of two parts; part 1 is a modified 3+3 dose-escalation design with five dose levels of SYSA1801 (0.5, 1, 2, 2.5 and 3 mg/kg) administered intravenously (IV) every 3 weeks (Q3W), followed by dose expansion at effective doses. Part 2 is a cohort expansion at the optimal dose. Here, we present the preliminary results of SYSA1801 for part 1. Results: As of Nov 5, 2022, 33 pts with a median age of 59 yrs (range 22-71) were enrolled to receive up to SYSA1801 3 mg/kg in part 1. 26 pts (78.8%) had gastric cancer (GC) and 7 pts (21.2%) had pancreatic cancer. ECOG PS was 0 in 5 pts (15.2%) and 1 in 28 pts (84.8%). 11 pts (33.3%) had been heavily pretreated ...