A pooled analysis of JSKN003, a biparatopic anti-HER2 antibody conjugate (ADC), in patients with advanced HER2-overexpressing (IHC 3+) gastrointestinal tumors.

作者：Dan Liu, Бо Лю, Zhen Li, Bo Gao, Xiao‐Chen Zhang, Jian Ruan, Jia Wei, John Park, Wenfeng Li, Hong Zong, Jing Dai, Qun Li, Jiong Wu, Jian Zhang, Guixiang Weng, Zhongmin Zhang, Ting Xu, Zhenjiu Wang, Ruyi Xu, Lin Shen · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.3022 · 被引用次数：5 · 研究领域：HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research、Gastric Cancer Management and Outcomes

3022 Background: JSKN003 is a biparatopic HER2-targeting ADC conjugated with a topoisomerase I inhibitor (TOP1i) payload via a dibenzocylooctyne tetrapeptide linker. The efficacy and safety of JSKN003 in several solid tumors have been highlighted in previous reports. Methods: JSKN003-101 and JSKN003-102 are dose escalation and expansion studies involving Australian and Chinese patients (pts) with metastatic solid tumors. This pooled analysis of two studies was performed to assess the efficacy and safety in advanced HER2-overexpressing (IHC 3+) gastric or gastroesophageal cancer (GC/GEJC) and colorectal cancer (CRC) pts. Results: As of data cutoff (18 Dec 2024), 40 patients with HER2-overexpressing (IHC 3+ by local lab) gastrointestinal tumor (23 in GC/GEJC and 17 in CRC) were enrolled across 7 dose levels: 2.1 mg/kg (n = 1), 4.2 mg/kg (n = 1), 5.2 mg/kg (n = 1), 6.3 mg/kg (n = 33), 7.3 mg/kg (n = 1), 8.4 mg/kg (n = 2), 10.5 mg/kg (n = 1). The median follow-up time of two studies was 7.16 months. Most pts were heavily pretreated (37.5% had ≥3 lines of prior treatment; 45.0% received irinotecan; 67.5% received anti-HER2 therapy; 42.5% received IO therapy). Four of the 17 CRC pts were RAF/RAS mutations (n = 2 RAS-mut, n = 2 RAF-mut). Thirty-nine patients had at least one tumor assessment after baseline. The overall response rate (ORR) per RECIST v1.1 in HER2-overexpressing gastrointestinal tumor was 66.7% and the disease control rate (DCR) was 94.7%. Among 22 GC/GEJC pts, the OR...