Efficacy and safety of infigratinib in locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients with FGFR2 gene amplification

The FGFR/FGF cascade is a complex intracellular pathway that controls cellular proliferation, tumor growth, angiogenesis, and dissemination. It is implicated in various human cancers including gastric cancer (GC). The FGFR2-amplification in a proportion ranging from 9% to 1.2% worldwide in GC patients. However, previous studies have demonstrated FGFR2-amplification may have poor PFS and OS survival in GC patients. Infigratinib (BGJ398) is a selective ATP-competitive, FGFR1–3 selective oral TKI. We present the data generated from the LB1001-201 trial (NCT05019794) Cohort 1 to evaluate the efficacy and safety of infigratinib monotherapy in previously systemic second-line treated patients harbouring FGFR2 gene amplification. Population and eligibility criteria - Failed on prior 2nd -lines treatment or above, locally advanced or metastatic GC/EGJ. FGFR2 gene amplification positive was confirmed via central FISH testing. Adequate organ function and laboratory values. MAPK-MEK or selective FGFR inhibitor treatment-naive. Procedures and treatment - Tumor biopsy or FFPE samples will be tested at the central lab for FGFR2 gene amplification orally infigratinib (125mg, QD) for 3 weeks on, 1 week off in each 28-day cycle; Dose adjustment will be based on drug-related AEs and severity per protocol demanded. Outcomes and assessments - ORR and DCR: Descriptive statistics were used, and an accurate 95% CI was provided. Time-to-event endpoints were summarized using K-M analyses. Safety endpoints were analyzed using frequency and percentage distribution in patients who received at least one dose of infigratinib. cORR 25.0% (95%CI 8.7, 49.1), DCR 80.0% (95%CI 56.3, 94.3), mDoR 3.8 months (mos) (3.6, NE). mPFS 3.3 mos (95%CI 2.3, 4.5), mOS 8.0 mos (95%CI 4.1, NE). 15/19 patients with tumor shrinkage, the maximum from baseline was -78.5%. ≥ Grade 3 TRAE was 42.9%, most were recoverable. No drug-induced death was reported. Infigratinib in GC/GEJ patients with FGFR2 gene amplification has shown an inspiring clinical improvement, with acceptable tolerance, which is a potential first TKI regimen that precisely targeting in this population.