JSKN003, a biparatopic HER2-targeting ADC, in heavily pretreated HER2-positive breast cancer: A pooled analysis of early-phase studies.

作者：Yiqun Du, Jian Zhang, Jieqiong Liu, Wenfeng Li, Qingyuan Zhang, Louisa L. Lo, Yongmei Yin, Yanxia Zhao, Zhixiang Zhuang, Xinshuai Wang, Xian Wang, Jian Huang, Hong Zong, Guixiang Weng, Zhongmin Zhang, Xiaochen Zhang, Jian Ruan, Zhen Li, Xiang Wang, Jiong Wu · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.1028 · 被引用次数：4 · 研究领域：HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research、Cancer Treatment and Pharmacology

1028 Background: JSKN003 is a biparatopic HER2-targeting antibody-drug conjugate (ADC) conjugated to a topoisomerase I inhibitor (TOP1i) via a tetrapeptide linker, designed to enhance serum stability and anti-tumor activity. The efficacy and safety of JSKN003 in advanced ovarian cancer and other solid tumors have been highlighted in previous reports, and this analysis provides updated insights into its performance in HER2-positive breast cancer. Methods: JSKN003-101 is a dose-escalation and -expansion study in Australia, and JSKN003-102 is a phase I/II study in China, both involving patients with advanced solid tumors. A pooled analysis was performed to assess its efficacy and safety in HER2-positive advanced breast cancer. Results: As of November 29, 2024, the median follow-up duration was 3.52 months (range: 2.99-3.71). A total of 71 patients with HER2-positive breast cancer were enrolled, with the majority receiving 6.3 mg/kg or 8.4 mg/kg doses. The median age was 54 years (range: 32-79), with 78.9% ECOG 1. All patients had stage IV disease, with 76.1% having visceral metastases. All patients had prior anti-HER2 therapy, including 87.3% with prior ADCs or TKIs, and 56.3% having ≥3 prior lines. Among 62 evaluable patients, 56 were T-DXd naïve. In these 56 patients, the overall response rate (ORR) was 67.9% (95%CI: 54-79.7), and the disease control rate (DCR) was 94.6% (95%CI: 85.1-98.9). In the RP2D subgroup (6.3mg/kg, n = 30), the ORR was 70.0% (95%CI:50.6-85.3). Of 6 pati...