The US Food and Drug Administration approved lirafugratinib (Lyrfigtu, Elevar Therapeutics, Inc.) on September 23, 2026, for the treatment of adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring a fibroblast growth factor receptor 2 (FGFR2) gene fusion or other rearrangement. The agency classified lirafugratinib as a kinase inhibitor and granted the application priority review; the drug also carries breakthrough therapy and orphan drug designations.
Approval was based on data from the single-arm REFOCUS trial, in which lirafugratinib produced an objective response rate of 46% and a median duration of response of 11.8 months by independent review. Because the trial was single-arm and lacked a comparator, the results cannot be interpreted as evidence of a survival benefit relative to alternative therapies.
Key finding
In the single-arm REFOCUS trial, lirafugratinib produced an objective response rate of 46% (95% CI: 36–55) with a median duration of response of 11.8 months (95% CI: 7.5–13.0) in previously treated patients with FGFR2-rearranged cholangiocarcinoma, though the absence of a control arm limits comparative interpretation of these findings.
Study Design
| Trial | REFOCUS (NCT04526106); multicenter, open-label, single-arm |
|---|---|
| Population | 116 adults with unresectable or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement, naïve to prior FGFR inhibitor treatment, and previously treated with chemotherapy or chemoimmunotherapy |
| Treatment | Lirafugratinib 70 mg orally once daily until disease progression or unacceptable toxicity |
| Primary endpoint | Objective response rate (ORR) and duration of response (DOR) by independent review committee per RECIST v1.1 |
The trial enrolled patients who had progressed on or were intolerant of prior chemotherapy or chemoimmunotherapy but had not previously received an FGFR inhibitor, reflecting a second- or later-line population in a genomically selected indication. The review was conducted under the FDA’s Real-Time Oncology Review pilot program and utilized an Assessment Aid voluntary submission from the applicant.
Results and Safety
Among 116 evaluable patients, the independent review committee determined an ORR of 46% (95% CI: 36, 55). Median duration of response was 11.8 months (95% CI: 7.5, 13.0). No additional efficacy endpoints, including progression-free survival or overall survival data, were reported in the FDA approval announcement.
The prescribing information includes warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity. Detailed adverse event rates, including the incidence and severity of individual toxicities, were not disclosed in the approval summary. Healthcare professionals are encouraged to report serious adverse events to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
Clinical Context
FGFR2 gene fusions and rearrangements occur in approximately 10–15% of intrahepatic cholangiocarcinomas and represent one of the most established actionable targets in biliary tract cancers. Lirafugratinib joins a class of approved FGFR inhibitors in this indication, though direct comparative data against other agents in the class are not available from REFOCUS, which was limited to patients who had not previously received FGFR-directed therapy.
The drug’s breakthrough therapy designation suggests the FDA considered preliminary evidence of substantial improvement over available therapy, but head-to-head data were not part of this submission. Clinicians selecting among agents in this class will need to weigh the available single-arm response data alongside tolerability profiles until comparative evidence emerges.
Sources
- US Food and Drug Administration. “FDA Approves Lirafugratinib for Previously Treated Unresectable, Locally Advanced or Metastatic Cholangiocarcinoma.” Regulatory approval summary. September 23, 2026. View source.
AI disclosure: This article was prepared with assistance from generative AI using the source material cited above. It was reviewed and edited by Brandon Twyford before publication.
