Abstract CT008: First-in-human study of SYS6010, a novel EGFR targeting antibody drug conjugate (ADC) for patients with advanced solid tumors

作者：Shun Lu, Zhen Zhou, Ziming Li, Zhiyong He, Jian Fang, Hongmei Sun, Yi Gong, Ying Cheng, Yi-Bing LIU, Yu Yao, Yu Yan, Yanhong Shang, Xianglin Yuan, Liang Han, Mingjun Zhang, Kunyu Yang, Liqiong Zhang, Xuechao Wan, Huanhuan Qi, Yang Yang · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.am2025-ct008 · 被引用次数：5 · 研究领域：HER2/EGFR in Cancer Research、Cancer Treatment and Pharmacology、Lung Cancer Treatments and Mutations

Abstract Background: SYS6010 is a novel ADC comprising of an anti-epidermal growth factor receptor (EGFR) humanized IgG1 monoclonal antibody conjugated to topoisomerase I inhibitor JS-1 via a cleavable glycine̶̶-glycine-phenylalanine-glycine tetrapeptide linker. Methods: This multicenter, open-label, phase 1 study evaluated the safety, tolerability and preliminary efficacy of SYS6010 in patients with advanced solid tumors who had failed or were intolerant to standard treatment. The study consisted of two parts, dose escalation, PK expansion (part 1) and dose expansion (part 2), part 1 used a 3+3 dose-escalation design with six dose levels of SYS6010 (0.6, 1.8, 3.6, 4.8, 5.6 and 6.4 mg/kg) administered intravenously every 3 weeks and PK expansion. Part 2 was dose expansion at effective doses identified in part 1. The primary endpoints were safety, maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Results: As of December 26, 2024, 232 patients received ≥ 1 dose of SYS6010. Most frequent cancer type was non-small cell lung cancer (NSCLC, n=137). The median (range) prior anti-cancer drug therapy regimen was 3 (1-11). One dose-limiting toxicity (grade 4 thrombocytopenia) occurred at 6.4 mg/kg. MTD was not reached. 213 (91.8%) patients had treatment-related adverse events (TRAEs) with ≥ grade 3 TRAEs at 47%. The most common (all grade/≥ grade 3) TRAEs were leukopenia (47.8%/20.7%), anemia (46.1%/7.3%), nausea (46.1%/0.9%), thrombocytopenia (44.8%/13.8%), neutropeni...