Novel TROP2 antibody–drug conjugates for treatment of HER2-negative metastatic breast cancer patients with brain metastases: a promising option☆

作者：Jian Wang, Yi Zhang, Rilan Bai, Yuan Wu, Zhongsheng Tong, A. Liu, Yi Zhang, Huimin Wang, Xianrui Wu, Ying Cheng, Hongjie Yang, Qing Zhou, Xixin Xing, Xian Chen, Fang Qiu, Fei Ma · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105059 · 被引用次数：5 · 研究领域：HER2/EGFR in Cancer Research、Brain Metastases and Treatment、Lung Cancer Research Studies

BACKGROUND: ESG401 is a further optimized antibody-drug conjugate comprising a humanized anti-trophoblast cell-surface antigen 2 immunoglobulin G1 monoclonal antibody conjugated to SN-38, a topoisomerase I inhibitor, via a proprietary novel stable linker. The analysis aimed to explore the efficacy of ESG401 in human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) patients with brain metastases (BMs), a population urging significant clinical need with limited systematic treatment options. PATIENTS AND METHODS: This subgroup analysis was conducted as part of an open-label, multi-dose, dose-escalation, and cohort-expansion multicenter phase I trial. Eligible participants were aged 18-75 years and had locally advanced or metastatic solid tumors. For this subgroup analysis, patients with histologically confirmed HER2-negative BC and BMs were enrolled. Efficacy endpoints included overall objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Intracranial-specific endpoints included intracranial ORR (iORR), intracranial DCR (iDCR), and intracranial PFS. This trial is registered at ClinicalTrials.gov, NCT04892342. RESULTS: Among 17 patients with efficacy-evaluable BMs, the iORR was 41% (7/17) [95% confidence interval (CI) 18.4% to 67.1%] including 3 patients achieving an intracranial complete response. The iDCR was 76% (13/17) (95% CI 50.1% to 93.2%). The overall ORR was 53% (9/17) (95% CI 27.8% to 77.0%), the overall DCR...