1539P - Efficacy and safety of perioperative chemotherapy combined with tislelizumab and trastuzumab for HER2-positive resectable gastric/gastroesophageal junction cancer (GC/EGJC): Preliminary results of a phase II, single-arm trial

Background

Immunotherapy combined with trastuzumab, and chemotherapy have been recommended by the clinical guidelines of many countries as the first-line treatment for advanced HER2-positive G/GEJ adnocarcinoma. Combining chemotherapy with tislizumab and trastuzumab in the neoadjuvant/adjuvant setting may benefit patients with locally advanced, resectable HER2-positive GC/GEJC.

Methods

This study is a multicentre, single-arm, open-label phase II study. Patients with histologically confirmed cT2-4NxM0 or cTxN+M0, (TNM 8th edition), resectable GC/GEJC are eligible for this study. Neoadjuvant therapy will be administered for four cycles. The patients will receive tislelizumab and trastuzumab for 1 cycle (Q3W), followed by tislelizumab and trastuzumab combined with DOS (Docetaxel + Oxaliplatin + S-1) for 3 cycles (Q3W). Surgery is planned 4-6 weeks after preoperative treatment. Patients will receive adjuvant therapy starting within 4–6 weeks after surgery for 9 cycles. The primary endpoint was pathological complete response rate (pCR). Secondary endpoints included R0 resection rate, 1-year and 2-year event-free survival (EFS), overall survival (OS) and safety.

Results

From September 13, 2021, to May 05, 2023, 18 patients were enrolled, and the median follow up time was 9.2 months (0.1-20.0).11 patients completed surgery, and 5 patients were undergoing neoadjuvant therapy, 2 patients required organ preservation therapy. R0 resection rate was 100%, 6 patients (54.5%) achieved pCR, and 7 patients (63.6%) achieved MPR. Postoperative pathology showed that T stage decreased in 9 cases after neoadjuvant therapy, with a decrease rate of 81.8%. Median OS and EFS have not been reached. The most common AEs (grade ≥3) were anaemia in 1 (5.6%) and neutropenia in 1 case (5.6%). The immune-related adverse events were all grade 1. No treatment related deaths were reported.

Conclusions

According to the preliminary results, tislelizumab combined with trastuzumab and standard chemotherapy in the perioperative period of HER2-positive GC / EGJ have a good clinical benefit trend and controllable security.

Clinical trial identification

NCT04819971.

Editorial acknowledgement

Legal entity responsible for the study

The First Affiliated Hospital of Zhengzhou University.

Funding

BeiGene (Beijing) Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.