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FDA approves lirafugratinib in pre-treated cholangiocarcinoma with FGFR2 fusions or rearrangements

On September 23, 2026, the U.S. Food and Drug Administration (FDA) approved lirafugratinib, an oral, selective FGFR2 inhibitor, for previously treated cholangiocarcinoma (CCA) harboring FGFR2 fusions or rearrangements.¹ Although first-line gemcitabine- and cisplatin-based therapy, with or without immunotherapy, can provide clinical benefit in CCA, disease progression is common and treatment options after first-line therapy remain limited. FGFR2 fusions and rearrangements occur in a subset of intrahepatic CCA, creating an opportunity for targeted treatment while highlighting the need for effective therapies with durable activity.2

The recent approval is supported by findings from the Phase I/II ReFocus trial (NCT04526106), which assessed the efficacy of lirafugratinib in 116 patients with advanced or metastatic CCA harboring FGFR2 fusions or rearrangements who had received prior systemic chemotherapy but had not received a prior FGFR inhibitor. Confirmed overall response rate (ORR) and duration of response (DOR) were the primary and key secondary endpoints respectively.3

Lirafugratinib achieved an objective response rate of 46.5% (95% CI, 37.1-56.1), including complete responses in 2.6% and partial responses in 43.9% of patients. The disease control rate was 96.5%, while median DOR was 11.8 months (95% CI, 7.5-13.0), with 76.2% of responses lasting longer than 6 months. The safety profile was consistent with FGFR2 inhibition, with palmar-plantar erythrodysesthesia and stomatitis among the most common grade ≥3 treatment-related adverse events.3

Approval of lirafugratinib represents a potential advance for FGFR2-altered CCA, offering a targeted treatment approach with substantial response rates and durable disease control in a population with limited options following first-line therapy.

References:

  1. U.S. Food and Drug Administration. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. Available here. (Last Accessed 24/09/2026).
  2. Vogel A, Sahai V, Hollebecque A, et al. An open-label study of pemigatinib in cholangiocarcinoma: Final results from fight-202. ESMO Open. 2024 Jun;9(6):103488. doi:10.1016/j.esmoop.2024.103488
  3. Hollebecque A, Borad MJ, Lu P, et al. Efficacy and safety of lirafugratinib in FGFR-naïve cholangiocarcinoma (CCA) patients harboring FGFR2 fusions/rearrangements (FGFR2 f/R). J Clin Oncol 2026 Jan 10;44(2_suppl):476–476. doi:10.1200/jco.2026.44.2_suppl.476