On September 23, 2026, the FDA approved lirafugratinib (Lyrfigtu), a next‑generation kinase inhibitor, for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement.

A Targeted Option for FGFR2‑Driven Disease 

FGFR2 rearrangements occur in approximately 10% to 15% of intrahepatic cholangiocarcinomas, making them one of the most actionable genomic alterations in this malignancy. Lirafugratinib joins a growing class of FGFR inhibitors but distinguishes itself through its clinical performance in a heavily pretreated population and its once‑daily dosing schedule.

The approval is based on results from REFOCUS (NCT04526106), a multicenter, open‑label, single‑arm trial evaluating lirafugratinib in 116 patients with unresectable or metastatic cholangiocarcinoma who had received prior chemotherapy or chemoimmunotherapy and were FGFR inhibitor–naive. Patients received lirafugratinib 70 mg orally once daily until disease progression or unacceptable toxicity.

Efficacy Outcomes: Meaningful Responses in a Difficult‑to‑Treat Setting 

The trial’s major efficacy end points—objective response rate (ORR) and duration of response (DOR)—were assessed by an independent review committee using RECIST v1.1.
Key findings include:

• ORR: 46% (95% CI, 36-55)
• Median DOR: 11.8 months (95% CI, 7.5-13.0)

Safety Profile and Key Precautions 

The safety profile of lirafugratinib aligns with known class effects of FGFR inhibition. The prescribing information includes warnings and precautions for:

• Ocular toxicity
• Hyperphosphatemia and soft tissue mineralization
• Embryo‑fetal toxicity

Recommended Dosage 

The recommended dose is lirafugratinib 70 mg orally once daily, continued until disease progression or unacceptable toxicity.
Full prescribing information will be available on Drugs@FDA.

Source 

US Food and Drug Administration. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. September 23, 2026. Accessed October 1, 20126. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lirafugratinib-previously-treated-unresectable-locally-advanced-or-metastatic