FDA Approves Lirafugratinib for Previously Treated FGFR2-Altered Cholangiocarcinoma
核心洞察
The FDA approved lirafugratinib (Lyrfigtu) on September 23, 2026, for adults with previously treated unresectable, locally advanced or metastatic FGFR2 (搜索)-altered cholangiocarcinoma (搜索).
Approval was supported by the single-arm phase 1/2 ReFocus trial, which reported a 46% objective response rate and an 11.8-month median duration of response.
Lirafugratinib is a highly selective, irreversible oral FGFR2 (搜索) inhibitor dosed at 70 mg once daily, and it previously held Breakthrough Therapy and Orphan Drug designations.
The US Food and Drug Administration approved lirafugratinib (Lyrfigtu) on September 23, 2026, for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma (搜索) harboring a fibroblast growth factor receptor 2 (FGFR2 (搜索)) gene fusion or other rearrangement. The agent is an oral small-molecule inhibitor of FGFR2 and previously received Breakthrough Therapy and Orphan Drug designations.
ReFocus Trial Results
Efficacy was evaluated in ReFocus (NCT04526106), a multicenter, open-label, single-arm phase 1/2 trial that enrolled 116 patients with unresectable or metastatic cholangiocarcinoma (搜索). Patients were naive to FGFR inhibitor treatment and had received prior chemotherapy or chemoimmunotherapy. All patients received lirafugratinib at 70 mg once daily until disease progression or unacceptable toxicity.
The major efficacy outcome measures were objective response rate and duration of response, both determined by an independent review committee according to RECIST v1.1. Objective response rate was 46% (95% CI, 36%-55%) and median duration of response was 11.8 months (95% CI, 7.5-13.0).
Results from the trial were most recently presented at the 2026 ASCO Gastrointestinal Cancers Symposium. In the FGFR inhibitor-naive cholangiocarcinoma (搜索) population that had received prior chemotherapy, lirafugratinib produced a confirmed objective response rate of 46.5% (95% CI, 37.1%-56.1%) by independent review committee assessment, with a disease control rate of 96.5% (95% CI, 91.3%-99.0%). Median progression-free survival was 11.3 months (95% CI, 9.2-14.8) and median overall survival was 22.8 months (95% CI, 18.1-27.2).
The safety profile was consistent with on-target FGFR2 (搜索) inhibition, and adverse effects observed in the trial were managed through dose adjustments.
Mechanism and Selectivity
Lirafugratinib is a potent, selective and irreversible oral small-molecule inhibitor of FGFR2 (搜索), a receptor tyrosine kinase frequently altered in cholangiocarcinoma (搜索) and other solid tumors. FGFR2 is one of four members of the FGFR family, a group of closely related proteins with highly similar sequences and properties. The drug's selectivity for FGFR2 over other family members is intended to differentiate it from earlier FGFR inhibitors.
Cholangiocarcinoma (搜索), also known as bile duct cancer, is a rare malignancy with approximately 8,000 new cases diagnosed annually in the United States.
Dosing and Safety Warnings
The recommended lirafugratinib dose is 70 mg orally 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.
Regulatory Timeline and Ongoing Development
The FDA granted priority review to lirafugratinib in this indication in March 2026 and set a Prescription Drug User Fee Act target action date of September 27, 2026. Elevar (搜索) submitted the new drug application in January 2026. The company has also submitted a marketing authorization application to the European Medicines Agency (搜索) seeking approval of lirafugratinib for the same indication.
Beyond cholangiocarcinoma (搜索), lirafugratinib is being evaluated in the phase 2 ReFocus202 trial (NCT07359820), which is enrolling patients with previously treated, advanced or metastatic solid tumors other than cholangiocarcinoma that harbor an FGFR2 (搜索) fusion or rearrangement and who have not received a prior FGFR inhibitor.