Intraperitoneal and intravenous paclitaxel plus S-1 and sintilimab as first-line treatment for gastric cancer with peritoneal metastasis: a single-arm phase 2 trial (DRAGON-09)

Background First-line PD-1 blockade plus chemotherapy has shown significant clinical benefit in metastatic gastric cancer. This study aimed to evaluate the efficacy and safety of sintilimab and S-1 plus intraperitoneal and intravenous paclitaxel as first-line treatment for patients with gastric cancer peritoneal metastasis (GCPM), as well as exploratory predictive biomarker analysis. Methods We conducted a single-arm, phase 2 trial at a single centre in China between Jan 1, 2022, and Dec 31, 2023. Patients with laparoscopically confirmed GCPM were treated with sintilimab (200 mg IV on D1), S-1 (40–60 mg orally twice a day for D1–14), and paclitaxel (20 mg/m 2 intraperitoneally and 50 mg/m 2 IV on D1 and 8), in cycles every 3 weeks. The primary efficacy endpoint was overall survival (OS) rate at 1 year. This study is registered with ClinicalTrials.gov, NCT05204173. Findings 38 patients were included. The median progression-free survival was 14.6 months (95% CI: 10.8–not reached [NR]) and OS was 18.4 months (95% CI: 15.0–NR). The post-hoc analysis showed the objective response rate was 57.9% and disease control rate was 94.7%. The most common treatment-related adverse events were anemia, glutamic oxaloacetic transaminase elevated, and leukopenia. Longitudinal analyses of plasma circulating tumor DNA showed that low baseline human genome equivalent was associated with favorable OS. Interpretation First-line sintilimab and S-1 plus intraperitoneal and intravenous paclitaxel showed promising therapeutic efficacy in patients with GCPM. Funding Natural Science Foundation of Shanghai, Shanghai Municipal Health Commission, National Science Foundation of China, and the Shanghai Hospital Development Center.