4030 Background: Tisle is an anti-PD-1 antibody. The combination of Tisle + XELOX/FP is a first-line treatment of AGC in China. Both irinotecan and paclitaxel have also shown antitumor activity in AGC. This Phase I/II study evaluated the efficacy and safety of Tisle + POFI in this population. Methods: This single-center, single-arm phase I/II study enrolled treatment-naïve patients with pMMR/MSS AGC, aged 18-75, who have at least one measurable lesion according to RECIST 1.1 and an ECOG PS of 0-1. Eligible participants received POFI (irinotecan/paclitaxel (mg/m2): 135/45 (dl #1), 150/45 (dl #2), 135/67.5 (dl #3), and 135/90 (dl #4), oxaliplatin 85 mg/m 2 , levoleucovorin 200 mg/m 2 , and 5-FU 2400 mg/m 2 for 46 hours every 2 weeks) in combination with Tisle 200mg every 2 weeks. The primary endpoint was the objective response rate (ORR) per RECIST 1.1. Results: As of Dec. 23, 2025, 47 patients were enrolled (median age: 58 years, range: 31–72; 26%(12/47) ECOG PS 1; 74% poorly differentiated; 68%(32/47) with ≥2 metastatic sites; 34% with programmed death-ligand 1 combined positive score PD-L1 CPS ≥1). The confirmed ORR was 76.6% (36/47), and the disease control rate was 95.7%. Median progression-free survival (PFS) was 11.1 months (95% CI: 8.8, 13.4) (versus 6.9 months (5.7-7.2) for ITT population for RATIONALE 305, ESMO 2023). Median duration of response was 9.7 months (95% CI: 6.7, 12.2). Median overall survival was 16.0 months (95% CI: 12.4, 23.0). All patients experienced treatment-emergent adverse events. The most common grade 3/4 adverse events included neutropenia (53.2%), leukopenia (27.7%), and anemia (21.3%). No new safety signals were identified. Conclusions: Tisle + POFI showed promising efficacy and a manageable safety profile as first-line treatment for HER2-negative, pMMR/MSS AGC, warranting further investigation. Clinical trial information: NCT05319639 .
Chen et al. (2026) studied this question.