First-in-human study of JSKN016, a bispecific anti-TROP2/HER3 antibody drug conjugate (ADC): Antitumor activity in patients (pts) with metastatic triple-negative breast cancer (mTNBC) and safety results.

作者：Herui Yao, Jieqiong Liu, Yinduo Zeng, Zhangzhou Huang, Jinglong Wang, Yu Cao, Ying Wang, Wenjing Wu, Yaping Yang, Fengyan Yu, Xiuping Lai, Hong Zong, Dongqing Lv, Junyan Wu, Suiwen Ye, Ting Xu, Zhenjiu Wang, Xiaowen Tang, Ruyi Xu, Erwei Song · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.e13138 · 被引用次数：9 · 研究领域：HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research、Radiopharmaceutical Chemistry and Applications

e13138 Background: TROP2 and HER3 are both highly expressed in TNBC and associated with worse survival. JSKN016 is a bispecific TROP2/HER3-targeting ADC developed with novel linker to conjugate the payload, a topoisomerase Ⅰ inhibitor with a drug-to-antibody (DAR) of 4. Methods: JSKN016-101 (NCT06592417) is an ongoing first-in-human (FIH), dose-escalation (0.5-11.5 mg/kg, BOIN design) and dose-expansion study of JSKN016 as monotherapy in patients (pts) with metastatic solid tumors conducted in China. Here, we report the preliminary antitumor activity in TNBC pts, the safety profile and PK characteristic of JSKN016. Results: As of data cutoff on Dec 23, 2024, 19 pts have been enrolled and been escalated to 8 mg/kg dose level, the maximal tolerated dose (MTD) was not reached. A total of 6 TNBC pts enrolled across 3 dose levels: 4 mg/kg Q3W (n = 3), 6 mg/kg Q3W (n = 1), 8 mg/kg Q3W (n = 2). The median age was 45.7 years (range 41-55), all pts were pretreated with standard of therapy (20% received ≥ 3 prior lines of systemic therapy). Among 5 efficacy-evaluable TNBC pts, the ORR was 80.0% with 4 partial response (PR) and 1 stable disease (SD) (showed 29.5% tumor shrinkage in target lesions from baseline at week 6). The PFS was not yet mature. There was one DLT occurred during dose-escalation, which was a grade 3 (G3) dermatitis acneiform at 8 mg/kg Q3W dose level. The most frequent treatment-related adverse events (TRAEs) were nausea, anemia, vomiting and oral mucositis. Notably,...