Tislelizumab (Tisle) combined with POFI (irinotecan, paclitaxel, oxaliplatin, and 5-FU/levoleucovorin) as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma (AGC): Update from a single-arm, open-label phase II trial (SYLT-023).

Abstract

377 Background: A Phase I study demonstrated that tislelizumab (Tisle) combined with POFI (irinotecan, paclitaxel, oxaliplatin, 5-fluorouracil/levoleucovorin) was tolerable with promising antitumor activity as first-line treatment for HER2-negative, proficient mismatch repair (pMMR)/microsatellite stable (MSS) advanced gastric/gastroesophageal junction adenocarcinoma (AGC) (Lin R, et al. ASCO-GI 2025). This Phase II study evaluated the efficacy and safety of Tisle + POFI in this population. Methods: This single-center, single-arm phase 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 135 mg/m 2 , paclitaxel 90 mg/m 2 , 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 Aug. 27, 2025, 32 patients were enrolled (median age: 57.5 years, range: 31–71; 28% ECOG PS 1; 75% poorly differentiated; 69% with ≥2 metastatic sites; 41% with programmed death-ligand 1 combined positive score [PD-L1 CPS] ≥1). The confirmed ORR was 71.9% (23/32), and the disease control rate was 93.8%. Median progression-free survival (PFS) was 11.1 months (95% CI: 8.8, 14.2) (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: 6.6, 12.5). Median overall survival was 16.0 months (95% CI: 12.4, NR). All patients experienced treatment-emergent adverse events. The most common grade 3/4 adverse events included neutropenia (56.25%), leukopenia (31.25%), and anemia (25.00%). 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 .