Disitamab vedotin (RC48), tislelizumab, and S-1 as first-line therapy for HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from the RCTS trial.

作者：Lian Liu, Li Song, Zimin Liu, Yanguo Liu, Kainan Li, Lei Cong, Fangli Cao, Aina Liu, Haiyan Liu, Ling Li, Linli Qu, Yi Zhai, Feng Wang, Jisheng Li, Duan‐Bo Shi, Jiahui Chu, Di Zhang, Zhaodi Nan, Qian Xu, Shulun Nie · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4059 · 被引用次数：8 · 研究领域：Gastric Cancer Management and Outcomes、Gastrointestinal Tumor Research and Treatment、Pancreatic and Hepatic Oncology Research

4059 Background: Anti-PD1 antibody has significantly improved survival in patients with HER2-overexpressing and PD-L1 combined positive score (CPS) ≥1 GC/GEJC when added to trastuzumab and chemotherapy. Recent trials revealed that HER2-targeted antibody-drug conjugates, including RC48 and Trastuzumab Deruxtecan, combined with anti-PD1 antibody, have also shown promising efficacy in this population. This study reports updated survival results of RC48 combined with tislelizumab and the oral fluoropyrimidine S-1 as first-line therapy for patients with HER2-overexpressing GC/GEJC. Methods: This single-arm, multicenter clinical trial enrolled patients with unresectable or metastatic HER2-overexpressing (IHC 3+ or 2+, regardless of FISH status) first-line GC/GEJC. Patients received RC48 (2.5 mg/kg), tislelizumab (200 mg), and S-1 (40-60 mg BID for 14 days) every 3 weeks until disease progression (PD) or intolerable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 57 patients from 9 centers were enrolled, 71.9% HER2 IHC 3+, 17.5% IHC 2+/FISH+, and 10.5% IHC 2+/FISH-. 14.9% and 36.2% had CPS≥5 and ≥1, respectively. Median follow-up was 11.8 months. In the intent-to-treat population, the confirmed ORR (cORR) was 89.4% (51/57, 95% CI: 78.5-96.0%), the median PFS (mPFS) was 12.7 months (95% CI: 10.9-NA), and the 18-month OS rate (18m-OSr) was 72.7% (95% CI: 60.0-88.5%). ...