Multicenter phase 2 trial of first-line disitamab vedotin, tislelizumab, and S-1 in HER2-overexpressing advanced G/GEJ adenocarcinoma

A multicenter phase 2 trial in China evaluated the efficacy and safety of disitamab vedotin (HER2-directed antibody-drug conjugate) combined with tislelizumb (PD-1 inhibitor) and S-1 chemotherapy as first-line therapy for patients with advanced HER2-overexpressing gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The primary endpoint was confirmed objective response per independent central review. The study enrolled 57 patients (median age 65 years; IHC 3+ 71.9%; IHC 2+/ISH+ 17.5%; IHC 2+/ISH- 10.5%; PD-L1 CPS <1 54.4%). The confirmed objective response rate was 89.5% (95% CI 78.5-96.0). The median follow-up was 28.2 months. The median progression-free survival, overall survival, and duration of response were 13.8 months (95% CI 10.3-24.0), 31.9 months (22.1-NR), and 13.3 months (9.6-NR). Grade ≥ 3 treatment-related adverse events occurred in 64.9% of patients. The authors conclude that first-line disitamab vedotin with tislelizumab and S-1 demonstrated remarkable antitumor activity and a manageable safety profile in HER-overexpressing advanced G/GEJ adenocarcinoma.