FGFR2 amplified gastric cancer may benefit from treatment with infigratinib, according to Phase 2 findings that demonstrated objective responses and manageable safety in heavily pretreated patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma.
FGFR2 Targeting Shows Clinical Activity
Fibroblast growth factor receptor 2 (FGFR2) has emerged as a promising therapeutic target because of its role in gastric cancer progression. Investigators evaluated infigratinib, a selective fibroblast growth factor receptor 1–3 tyrosine kinase inhibitor, in a Phase 2 trial involving patients with FGFR2 amplified gastric cancer or gastroesophageal junction adenocarcinoma whose disease had progressed after at least two prior lines of systemic therapy for locally advanced or metastatic disease.
A total of 21 patients received oral infigratinib at a dose of 125 mg once daily on a schedule of 3 weeks on treatment followed by 1 week off treatment. The study assessed antitumour activity and safety in this molecularly selected population.
The results demonstrated preliminary clinical activity. The confirmed objective response rate was: 23.8% (95% CI: 8.2–47.2). Median progression free survival was 3.4 months, while median overall survival was 6.7 months.
Safety Profile in Advanced Disease
Safety findings suggested that treatment was generally manageable in this heavily pretreated population. The most common Grade 3–4 adverse events were elevated aspartate aminotransferase levels, decreased white blood cell count, and neutropenia.
Importantly, no treatment related deaths were reported during the study. These findings indicate that infigratinib can be administered with an acceptable safety profile in patients with advanced disease who have limited treatment options.
Resistance Mechanisms Require Further Study
Investigators also conducted exploratory genomic analyses to better understand mechanisms associated with disease progression. These analyses identified genetic alterations in individual patients whose disease progressed while receiving treatment.
However, the researchers noted that these observations were derived from a limited number of cases. As a result, the data should be considered hypothesis generating rather than definitive evidence of resistance pathways.
Overall, the findings support continued investigation of targeted approaches for FGFR2 amplified gastric cancer and gastroesophageal junction adenocarcinoma. The authors highlighted the need for larger studies, improved biomarker selection strategies, and more comprehensive characterisation of resistance mechanisms to optimise the clinical use of fibroblast growth factor receptor targeted therapies in this setting.
Reference
Yuan J et al. Efficacy and safety of infigratinib in patients with refractory advanced gastric or gastroesophageal junction adenocarcinoma harboring FGFR2 gene amplification: a single-arm, multicenter phase 2 trial. British Journal of Cancer. 2026;DOI:10.1038/s41416-026-03511-0.
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