FDA Approves Lirafugratinib for Previously Treated FGFR2-Altered Cholangiocarcinoma
Clinical Summary:
- Regulatory Update: The FDA has approved lirafugratinib for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement.
- Key Outcomes: In the single-arm REFOCUS study, lirafugratinib produced an objective response rate of 46% among patients with FGFR inhibitor–naïve cholangiocarcinoma previously treated with chemotherapy or chemoimmunotherapy. Median duration of response was 11.8 months.
- Clinical Relevance: This approval provides an additional biomarker-directed treatment option for previously treated FGFR2-altered cholangiocarcinoma, reinforcing molecular testing as an important component of treatment selection in advanced disease.
The US Food and Drug Administration (FDA) has approved lirafugratinib (Lyrfigtu; Elevar Therapeutics, Inc.) for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma harboring a fibroblast growth factor receptor 2 (FGFR2) gene fusion or other rearrangement.
This approval was based on results from the open-label, single-arm REFOCUS trial, which enrolled 116 patients with unresectable or metastatic cholangiocarcinoma who had not previously received an FGFR inhibitor and had received prior chemotherapy or chemoimmunotherapy to receive 70 mg of once daily lirafugratinib until disease progression or unacceptable toxicity.
The primary end points included objective response rate (ORR) and duration of response, as assessed via independent review according to RECIST v1.1.
At analysis, lirafugratinib produced an ORR of 46%. Median duration of response was 11.8 months, demonstrating sustained responses among patients who responded to treatment.
The recommended dose of lirafugratinib is 70 mg administered once daily until disease progression or unacceptable toxicity.
The prescribing information includes warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.
Lirafugratinib was previously granted Priority Review and received Breakthrough Therapy and Orphan Drug designations. These findings establish the activity of lirafugratinib in previously treated, FGFR inhibitor–naïve cholangiocarcinoma harboring an FGFR2 fusion or rearrangement and provide an additional targeted treatment option for this molecularly defined population.
Source:
US Food and Drug Administration. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. Accessed on September 23, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lirafugratinib-previously-treated-unresectable-locally-advanced-or-metastatic
