Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S-1 for neoadjuvant therapy of locally advanced gastric cancer with HER2 overexpression: Preliminary results of a prospective, single-arm, phase II study.

e16147 Background: The perioperative treatment of gastric and gastroesophageal junction (GC/GEJ) adenocarcinoma is being investigated through a combination of HER2-targeted therapy, immunotherapy, and chemotherapy. Disitamab vedotin (RC48), a HER2-directed antibody-drug conjugate (ADC), has shown significant anti-tumor efficacy and safety profiles. Furthermore, existing data indicate that the combination of RC48 with immunotherapy may produce a synergistic effect. Consequently, we conducted this study to evaluate the effects of combining RC48 with camrelizumab and S-1 in the neoadjuvant setting for patients with locally advanced, resectable GC/GEJ adenocarcinoma who exhibit HER2 overexpression. Methods: In this prospective phase II, single-arm study, we included patients with histologically confirmed, resectable GC/GEJ staged as cT3-4aN1-3M0 according to the TNM 8th edition, and exhibiting HER2 overexpression (IHC 3+ or IHC 2+). Participants received three cycles of treatment administered on a three-weekly schedule (Q3W). Surgical resection was planned to occur 3-4 weeks after the completion of neoadjuvant therapy. The primary endpoint was the pathological complete response (pCR) rate, while the secondary endpoints included the major pathological response (MPR) rate, clinical downgrading rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Sep. 18, 2022 to Dec. 12, 2024, a total of 32 patients were enrolled in the study. Two patients declined therapy after 2 cycles of neoadjuvant treatment, and five patients refused surgery after 3 cycles of neoadjuvant treatment. The objective response rate during neoadjuvant therapy was 80.0% (24/30). Among the 24 patients who underwent D2 resection, eleven (45.8%) achieved an MPR, including six (25%) with a pCR (ypT0N0M0). The R0 resection rate was 100%. The median DFS and OS have not been reached. The most common reported AEs (grade≥3) were decreased neutrophil count (10%), bowel obstruction (5%), ALT increased (5%) and AST increased (5%). There have been no treatment-related mortalities documented. Conclusions: The preliminary findings indicate that the neoadjuvant combination of RC48, camrelizumab and S-1 presents a promising and safe treatment option for locally advanced resectable GC/GEJ adenocarcinoma with HER2 overexpression. Clinical trial information: ChiCTR2300075446 .