Sintilimab combined with short-course intensified chemotherapy regimen nab-POF in the treatment of metastatic gastric cancer (FDZL-GC002): A single-arm, phase 2 trial.

Abstract

4057 Background: This prospective phase II study investigates a novel therapeutic strategy combining PD-1 inhibitor sintilimab (Sin) with short-course intensified chemotherapy regimen Nab-POF as first-line treatment for metastatic gastric cancer (MGC), based on the hypothesis that short-duration, high-intensity chemotherapy may potentiate antitumor immunity while reducing the cumulative immunosuppressive burden of prolonged chemotherapy. Methods: Eligible patients (pts) received Sin (200mg IV), nab-paclitaxel (125mg/m²), oxaliplatin (85mg/m²), and fluorouracil (2400mg/m² as a 48-hour infusion) (plus trastuzumab for HER2+ pts) Q2W. After 6 cycles, pts without disease progression received maintenance treatment (capecitabine + Sin). Upon disease progression, HER2- pts underwent reinduction with the Nab-POF regimen ± Sin, for up to 6 cycles, followed by maintenance therapy (S-1 +/- Sin). Tumor response was assessed every 3 cycles. PFS1 was defined as the time from informed consent to first progression. PFS2 was defined as the time from consent to second progression. If reinduction therapy was not performed, PFS2 equals to PFS1. The primary endpoint was PFS2 in HER2- pts. Results: In total, 123 pts were enrolled up to 09/2025. 118 pts were evaluable. This report presents the results for the HER2- population. Among 90 HER2- pts, the median age was 60 (23-83), with 72.2% male. The common metastatic sites included the liver (36.7%), peritoneum (26.7%), bone (13.3%), and lungs (6.7%). ORR was 82.2% (74/90) and DCR was 100%. Nine pts received complete response and CR rate was 10.0%. 2-year DFS and OS rate were both 100% among pts with CR. 60 pts progressed and 47 patients died. 25 pts experienced reinduction with the Nab-POF regimen ± Sin. Median PFS1 was 13.6mo (95%CI 9.8-16.1) and median PFS2 was 16.2mo (95%CI 11.0-23.2). Median OS was 21.3mo (95%CI 11.3-NR). 1-year OS rate was 72.2% (95%CI 63.5-82.1) and 2-year OS rate was 44.2% (95%CI 33.9-57.6). Subgroup analysis showed whether signet ring cells are present or not, whether liver metastasis occurs or not, and the level of CPS were not related to the therapeutic effect. All pts experienced treatment-related adverse events (AEs). Grade 3/4 AEs were 55.6% (50/90) and neutrophil decrease was the most common at 36.7% (33/90). Immune-related AEs occurred in 22(24.4%) pts, including 6 (6.7%) grade 3/4 events, which were effectively controlled. Conclusions: Sin plus short-course intensified chemotherapy regimen Nab-POF demonstrates high response and CR rate, and remarkable long-term effects. This approach may represent a feasible first-line treatment strategy, warranting further evaluation in randomized trials. Clinical trial information: NCT05982301 .