Updated results from the phase Ib/II study of fruquintinib combined with SOX and toripalimab in patients with advanced metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC).

423 Background: The efficacy of first-line treatment in advanced GC/GEJC patients (pts) with negative or low PD-L1 expression still needs to be improved. This phase Ib/II, open-label study (NCT05024812) evaluating fruquintinib (a highly selective VEGFR-1, -2, -3 inhibitor) plus toripalimab (anti-PD-1), and SOX has shown preliminary antitumor activity as first-line therapy in GC/GEJC. Here we update the results with longer follow-up duration 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/m 2 , 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: As of August 15, 2024, 32 pts (9 in phase Ib; 23 in phase II) had been enrolled. Pts characteristics included: median age 62 (range 38–73); 66% male; 88% with ECOG PS 1, and 31% with liver metastasis. 31 pts had PD-L1 CPS available. 40.6% were CPS < 1 and 68.8% were CPS < 5. Of the 30 pts evaluable for tumor response, the ORR was 63.5% (95% CI 43.9–80.1) with 4 pts achieving complete responses and DCR was 96.7% (95% CI 82.8–99.9). After a median follow-up of 10.94 months, the median PFS was 9.33 (95% CI: 5.68–NA) months and OS result was not reached. Pts with CPS < 5 were more likely to achieve higher response rate (65.0 vs 55.6%) and longer PFS than CPS ≥5 (12.68 vs 8.11 months). Similar trends were observed in pts with CPS < 1 and CPS ≥1 (ORR: 75.0 vs 52.9%; PFS: 12.68 vs 8.11 months). Treatment-related adverse events (TRAEs) were mainly grade 1-2 and the most common ones were hypoalbuminemia (50%), neutrophil count decreased (34%), anemia (41%), platelet count decreased (34%) and white blood cell decreased (34%). Grade 4 TRAEs occurred in 2 pts (impaired liver function, hypertriglyceridemia). There were no treatment related deaths in the trial. Conclusions: Fruquintinib combined with SOX and toripalimab provided favorable efficacy and manageable toxicity profile as first-line therapy for pts with advanced metastatic GC/GEJC, especially in pts with negative or low PD-L1 expression. More data including the potential predictive response biomarkers would be further analyzed and reported. Clinical trial information: NCT05024812 .