HIPEC combined with NIPS and tislelizumab for conversion therapy in gastric cancer with peritoneal metastasis (P0CY1 or PCI ≤10): A prospective, single-arm, phase II study.

Abstract

TPS4240 Background: Peritoneal metastasis, which is common, difficult to diagnose early, and associated with a poor prognosis, is a leading cause of death in pts with advanced gastric cancer. Due to the peritoneal-plasma barrier, traditional systemic chemotherapy is often ineffective for gastric cancer patients with peritoneal metastasis. In recent years, combined systemic and intraperitoneal therapy has gained increasing recognition. The RATIONALE-305 study demonstrated that tislelizumab (TIS) significantly improves outcomes in these patients. This study combines hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal and systemic chemotherapy (NIPS), and PD-1 inhibitor, exploring a novel conversion therapy regimen for pts with gastric cancer peritoneal metastasis. Methods: This is a prospective, single-center, single-arm phase II study aims at evaluate the efficacy and safety of HIPEC combined with NIPS and tislelizumab as conversion therapy for gastric cancer pts with peritoneal metastasis who are either cytology-positive only without macroscopic peritoneal deposits (P0CY1) or Peritoneal Carcinomatosis Index (PCI) ≤10. Key inclusion criteria are: 1) age 18-75 years; 2) ECOG performance status 0-1; 3) HER2-negative confirmed by IHC, and PD-L1 CPS≥1; 4) either P0CY1 or PCI ≤10 without other distant metastases confirmed by laparoscopy; 5) adequate function of major organs. Pts undergo diagnostic laparoscopy for PCI scoring and peritoneal cytology examination. Upon confirmation of eligibility, pts receive three sessions of HIPEC followed by 4 cycles of NIPS combined with systemic therapy. The HIPEC regimen consists of paclitaxel at a dose of 75 mg/m² administered on D1, 3, and 5. After a two-week rest, NIPS combined TIS is initiated. The NIPS regimen includes paclitaxel (20 mg/m², ip, D1,8, Q3W and 50 mg/m², iv, D1,8, Q3W) ,S-1 (40-60mg based on BSA, po, D1-14, Q3W). The dosage and administration of TIS is 200 mg, iv, D1, Q3W. Radiological evaluations are performed every 2 cycles during conversion therapy. Upon completion of conversion therapy, pts undergo a second laparoscopic exploration with peritoneal cytology examination to re-evaluate disease status. Operable pts who achieve R0 resection receive postoperative adjuvant therapy with the same regimen (paclitaxel + S-1 + TIS) for 4 cycles. For inoperable pts or those not achieving R0 resection, subsequent treatment is determined by a multidisciplinary team (MDT). The primary endpoint is the surgical conversion rate. Secondary endpoints include the 1-year progression-free survival (PFS) rate, 2-year overall survival (OS) rate, PFS, OS, and safety. Exploratory endpoints aim to investigate the correlation between efficacy prediction and biomarkers such as PD-L1 expression, CLDN18.2 expression, and microsatellite instability (MSI) status. Clinical trial information: NCT07304258 .