1467P - 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

Background

Disitamab vedotin (RC48), a HER2-directed antibody-drug conjugate (ADC), demonstrated significant anti-tumor activity. Moreover, data suggest that the combination of RC48 with immunotherapy exhibits a synergistic effect. Therefore, we conducted the study to investigate the effects of combining RC48 with camrelizumab and S-1 in the neoadjuvant setting for locally advanced, resectable GC/GEJC with HER2 overexpression.

Methods

In this prospective, phase II, single-arm study, we included patients with histologically confirmed, resectable gastric/gastric junction adenocarcinoma (GC/GEJ) staged as cT3-4aN1-3M0 according to the TNM 8th edition, and demonstrating HER2 overexpression (IHC 3+ or IHC 2+). Participants received three cycles of treatment on a three-weekly basis (Q3W). Surgical resection was scheduled to occur 3-4 weeks following the completion of neoadjuvant therapy. The primary endpoint was the pathological complete response (pCR) rate; 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 and May 5, 2024, a total of 28 patients were enrolled. Three patients had not completed neoadjuvant treatment. 5 patients refused surgery due to organ preservation. 4 patients refused study therapy after 2 cycles of neoadjuvant treatment. 16 patients who experienced D2 resection, 8 (8/16, 50%) achieved MPR, including 5 (5/16, 31.25%) with pCR (ypT0N0M0).The R0 resection rate was 100%. 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 suggest 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 identification

ChiCTR2300075446.

Editorial acknowledgement

Legal entity responsible for the study

J. Chai.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.