Disitamab vedotin (DV) plus toripalimab (Tor) and chemotherapy (C)/trastuzumab (Tra) as first-line (1L) treatment of patients (pts) with HER2-expressing locally advanced or metastatic (la/m) gastric cancer.

作者：Lin Shen, Zhi Peng, Changzheng Li, Linzhi Lu, Xiang Wang, Jun Zhang, Yanqiao Zhang, Ting Deng, Meili Sun, Dongyan Cai, Yin Jin, Hong Zong, Feng Ye, Huiting Xu, Mingjun Zhang, Jianzhi Liu, Dan Feng, Jianmin Fang · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.17_suppl.lba4012 · 被引用次数：9 · 研究领域：Gastric Cancer Management and Outcomes、HER2/EGFR in Cancer Research、Lung Cancer Treatments and Mutations

LBA4012 Background: DV+T showed encouraging efficacy with manageable safety for pts with HER2-expressing gastric or gastroesophageal junction (G/GEJ) cancer in the second- and later-line setting in a phase 1 trial (Wang et al, eClinicalMedicine, 2024). Here, we first report the efficacy and safety of 1L DV+Tor+C/Tra in pts with HER2-postive or HER2-low la/m G/GEJ cancer from the randomized phase 2 part of a seamless phase 2/3 trial. Methods: Pts with previously untreated HER2-positive (IHC 3+, or IHC 2+/FISH+) la/m G/GEJ cancer were randomized (1:1:1) to receive DV (2.5 mg/kg, Q2W) + Tor (3.0 mg/kg, Q2W) + CAPOX (oxaliplatin [OX]: 130 mg/m 2 , day 1; capecitabine [CAP]: 1000 mg/m 2 , days 1-14; Q3W) (experimental group [EG] 1), or DV + Tor +Tra (staring dose of 8 mg/kg followed by 6 mg/kg, Q3W) (EG2), or Tor + Tra + CAPOX (control group [CG] 1). For pts with HER2-low (IHC 1+, or IHC 2+/FISH-) la/m G/GEJ cancer, they were initially randomized (1:1) to receive DV (2.5 mg/kg) + Tor + CAPOX (EG1), or Tor + CAPOX (CG1) in stage 1; based on the safety data from stage 1, stage 2 was designed to randomize pts (1:1:1) to receive DV (2.5 mg/kg) + Tor + CAPOX (reduced dose: OX 100 mg/m 2 ; CAP 750 mg/m 2 ) (EG2), or DV (2.0 mg/kg) + Tor + CAPOX (reduced dose) (EG3), or Tor + CAPOX (CG2). The primary endpoint was objective response rate (ORR). Results: By date cutoff (Feb 7, 2025), 51 HER2-positive pts (mostly being HER2 IHC 3+) and 93 HER2-low pts (mostly being HER2 IHC 1+) were enrolle...