Final results of a phase II study of fruquintinib plus sintilimab as a second-line therapy for advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC).

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395 Background: Second-line treatment options for advanced gastric cancer remain limited. This open-label, single-arm phase II study (NCT05625737) aimed to identify the efficacy and safety of fruquintinib (VEGFR-1, -2, -3 inhibitor) plus sintilimab (anti-PD-1) as second-line therapy in GC/GEJC. Here we report the final results with a focus on subgroup analyses. Methods: Patients (pts) aged 18-75 years who were HER2-negative and had failed first-line standard treatment were enrolled. Eligible pts received 4mg of fruquintinib orally once daily on days 1-14 and 200 mg of sintilimab intravenously on day 1, with treatment repeated every 3 weeks. An optimal Simon two-stage design was employed. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: At data cut-off (April 10, 2025), 29 pts (7 in the first stage; 22 in the second stage) were enrolled. 69% had lymph node metastasis and 72.4% had previously received immunotherapy. Of the 24 pts evaluable for tumor response, the ORR was 37.5% with 9 pts achieving partial responses and DCR was 66.7%. At the final analysis with a median follow-up of 29.5 months, the median PFS was 5.1 months and the median OS was 12.7 months. Pts with lymph node metastasis were more likely to achieve higher response rate (52.9 vs 0%) and longer PFS than those without lymph node metastasis (5.1 vs 2.6 mon, P=0.1003). The median OS of pts with lymph node metastasis was significantly longer than that of pts without lymph node metastasis (14.9 vs 8.2 mon, P=0.0388). Similar trends were observed in pts without prior immunotherapies and with prior immunotherapies (ORR: 50 vs 31.3%; PFS: 6.2 vs 5.1 mon, P=0.515; OS: 25.1 vs 9.4 mon, P=0.0808). Only 4% (1 patient) patients experienced grade 3 or higher adverse events, including grade 3 elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and grade 4 bilirubin elevation. No serious treatment-related adverse events or treatment-related deaths were reported. Conclusions: Fruquintinib combined with sintilimab provided favorable efficacy and manageable toxicity profile as second-line therapy for pts with advanced GC/GEJC, especially in pts with lymph node metastasis or without prior immunotherapies. Further studies in larger cohorts to validate these findings are warranted. Clinical trial information: NCT05625737 .

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