Phase 1a study of ESG401, a Trop2 antibody-drug conjugate, in patients with locally advanced/metastatic solid tumors

作者：Jiani Wang, Zhongsheng Tong, Yinuo Tan, Yehui Shi, Yun Wu, Qing Zhou, Xiaoyan Xing, Xiaomei Chen, Fuming Qiu, Fei Ma · 发表于：Cell Reports Medicine · 年份：2024 · DOI：10.1016/j.xcrm.2024.101707 · 被引用次数：12 · 研究领域：HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research、Cancer Treatment and Pharmacology

This phase 1a study assesses ESG401 in patients with heavily pretreated locally advanced or metastatic solid tumors, focusing on metastatic breast cancer. Forty patients are enrolled: three experience dose-limiting toxicities, establishing the maximum tolerated dose at 16 mg/kg on days 1, 8, and 15 of a 28-day cycle. The most common grade ≥3 treatment-related adverse events are neutropenia and leukopenia. Among 38 efficacy-evaluable patients, the objective response rate (ORR) is 34.2%, the disease control rate (DCR) is 65.8%, and the clinical benefit rate (CBR) is 50.0% (including stable disease for at least 6 months). The median progression-free survival is 5.1 months, and the median duration of response is 6.3 months. In patients receiving therapeutically relevant doses, the ORR, DCR, and CBR are 40.6%, 75.0%, and 56.3%, respectively. ESG401 demonstrates a favorable safety profile and promising antitumor activity in this heavily treated population. The trial is registered at ClinicalTrials.gov ( NCT04892342 ). • ESG401 is a Trop2-targeting antibody-drug conjugate with a stable linker • Multiple dose levels and two regimens are assessed • ESG401 is well tolerated with a favorable safety profile • ESG401 demonstrates promising antitumor activity in heavily treated solid tumors Wang et al. report the safety and preliminary antitumor efficacy of an optimized Trop2-targeting antibody-drug conjugate, ESG401, in patients with heavily pretreated locally advanced or metastatic solid...