Phase Ib/II study of fruquintinib combined with SOX and toripalimab in advanced metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC).

Abstract

369 Background: There is an unmet need to improve the efficacy of first-line treatment in advanced GC/GEJC pts with negative or low PD-L1 expression. This Ib/II, open-label study (NCT05024812) aimed to identify the efficacy and safety of fruquintinib (VEGFR-1, -2, -3 inhibitor) plus toripalimab (anti-PD-1), and SOX as first-line therapy in GC/GEJC. Here we update the survival results and a specific focus on PD-L1 CPS features. Methods: The study of phase Ib employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) po, d1-14 , in combination with fixed dose of toripalimab (240mg, iv, d1), oxaliplatin (130 mg/m2, iv, d1) and S-1 (40-60mg based on BSA, po, d1-14) every 3 weeks. It had been reported in phase Ib that fruquintinib 5mg/d was defined as the RP2D. In phase II, a further 64 pts would be treated with the same regimen. Primary endpoint of phase II was PFS per RECIST 1.1. Secondary endpoints included ORR, DCR, OS, DOR and safety. Results: The data cut-off date was April 2025, 44 pts (9 in phase Ib; 35 in phase II) were enrolled. 43 pts had PD-L1 CPS available. 40.9% were CPS＜1 and 72.7% were CPS＜5. Of the 43 pts evaluable for tumor response, the ORR was 58.1% with 3 pts achieving complete responses and DCR was 95.3%. After a median follow-up of 12.09 months, the mPFS was 10.25 (95% CI: 5.91–NA) months and the mOS was still immature. The estimated 12-month and 18-month OS rate were 64% and 42%, respectively. Pts with CPS ＜1 were more likely to achieve higher response rate (76.5 vs 44.0%) and higher 9-month PFS rate than CPS ≥1 (81 vs 46%). Most TRAEs were grade 1-2 and grade ≥3 TRAEs occurred in 38.6% of pts. The most frequent grade 3 to 4 TRAEs were neutrophil count decreased (6.8%) and impaired liver function (6.8%). Conclusions: Fruquintinib combined with SOX and toripalimab provided promising efficacy and manageable toxicity profile as first-line therapy for pts with advanced metastatic GC/GEJC, especially in pts with negative PD-L1 expression. More data including the potential predictive response biomarkers would be further analyzed and reported. Clinical trial information: NCT05024812 .