New FDA Approval in Advanced Cholangiocarcinoma: Lirafugratinib (Lyrfigtu) for Patients With FGFR2 Fusions
The FDA has approved lirafugratinib for patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma (bile duct cancer) whose tumors harbor an FGFR2 gene fusion or other rearrangement. In the REFOCUS trial, the objective response rate was 46% and the median duration of response was 11.8 months.
23 September 2026 — The U.S. Food and Drug Administration (FDA) approved the targeted smart drug lirafugratinib (Lyrfigtu), a kinase inhibitor, for the treatment of patients with previously treated, surgically unresectable, locally advanced or metastatic cholangiocarcinoma (bile duct cancer).
The approval covers adult patients whose tumors harbor a fibroblast growth factor receptor 2 (FGFR2) gene fusion or other genetic rearrangement. The application was granted Priority Review, and lirafugratinib also received Breakthrough Therapy and Orphan Drug designations.
The REFOCUS Trial and Efficacy Data
The FDA's decision is based on efficacy data from REFOCUS (NCT04526106), a multicenter, open-label, single-arm clinical trial. The trial enrolled 116 patients who had previously received chemotherapy or chemoimmunotherapy but had never been treated with any FGFR inhibitor (FGFR inhibitor-naïve). Patients received lirafugratinib 70 mg once daily until disease progression or unacceptable toxicity.
Responses were assessed by an independent review committee according to RECIST v1.1 criteria:
- Objective Response Rate (ORR): A tumor response was observed in 46% of patients.
- Median Duration of Response (DOR): Among patients who responded to treatment, the response lasted a median of 11.8 months.
Clinical Use, Genomic Profiling and Toxicity Management
Because lirafugratinib is used only in patients whose tumors harbor an FGFR2 gene fusion or other rearrangement, the tumor needs to be examined for these alterations by genomic profiling before a treatment decision is made.
| Topic | Details |
|---|---|
| Patient selection | FGFR2 gene fusion or other rearrangement in the tumor (previously treated adult patients) |
| Dose | 70 mg, once daily, orally |
| Duration of treatment | Until disease progression or unacceptable toxicity |
The key warnings in the safety profile of the FDA-approved label are:
- Eye (ocular) toxicity
- Hyperphosphatemia (high blood phosphate levels) and soft tissue mineralization
- Embryo-fetal toxicity
💬 Important Information for Our Patients
Although the next-generation targeted smart drug described in this article has been approved by the U.S. Food and Drug Administration (FDA), the official licensing and Social Security Institution (SGK) reimbursement status of the drug in Turkey may vary depending on the active substance. Our clinic plans individualised treatment by sharing openly with our patients the legal conditions of access and the clinical availability in our country of innovative treatments of this kind identified through molecular analysis.
Conclusion
Lirafugratinib has become a new targeted option for previously treated patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement. A response in roughly half of FGFR inhibitor-naïve patients, lasting a median of 11.8 months, shows once again how important it is during diagnosis to examine the tumor genomically for FGFR2 alterations when planning treatment.
References
- U.S. Food and Drug Administration (FDA). (23 September 2026). FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma.