The U.S. 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 kinase inhibitor is indicated for patients who have already received prior systemic therapy.
The approval was supported by data from the REFOCUS trial, in which lirafugratinib produced an objective response rate of 46% with a median duration of response of 11.8 months in a single-arm, open-label study of 116 patients. As with all single-arm trials, the absence of a comparator arm limits direct conclusions about efficacy relative to other available agents.
Key finding
In the single-arm REFOCUS trial, lirafugratinib achieved a 46% objective response rate with a median duration of response of 11.8 months in previously treated patients with FGFR2-rearranged cholangiocarcinoma.
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 FGFR inhibitor treatment, who had received prior 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) as assessed by independent review committee per RECIST v1.1 |
REFOCUS enrolled patients who had progressed on or were intolerant of prior chemotherapy or chemoimmunotherapy and had not previously received an FGFR inhibitor. The trial was conducted across multiple centers in an open-label fashion, and responses were adjudicated by an independent review committee using RECIST v1.1 criteria. No randomized comparator arm was included in this efficacy analysis.
Results and Safety
Among the 116 evaluable patients, the independent review committee determined an ORR of 46% (95% CI: 36, 55) and a median DOR of 11.8 months (95% CI: 7.5, 13.0). No additional efficacy outcomes, such as progression-free survival or overall survival, were reported in the FDA approval announcement.
The prescribing information for lirafugratinib includes warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity. Detailed adverse event frequencies and severity grades were not disclosed in the FDA approval communication. Healthcare professionals are encouraged to consult the full prescribing information on Drugs@FDA for a complete safety profile.
Clinical Context
Cholangiocarcinoma remains a difficult-to-treat malignancy with limited options following frontline chemotherapy or chemoimmunotherapy. FGFR2 gene fusions and rearrangements occur in a subset of intrahepatic cholangiocarcinoma cases, and their identification has become an actionable target in this disease. Lirafugratinib joins a small class of FGFR inhibitors that have received approval in this molecularly defined population, reflecting a continued shift toward biomarker-driven therapy in biliary tract cancers.
The approval was supported through several FDA expedited pathways, including breakthrough therapy designation, orphan drug designation, and priority review, and was processed under the Real-Time Oncology Review program. Questions that remain unanswered from available data include how lirafugratinib compares to other approved FGFR inhibitors in this setting and its efficacy in patients who have progressed on prior FGFR-targeted therapy, a population that was excluded from REFOCUS.
Sources
- U.S. Food and Drug Administration. “FDA Approves Lirafugratinib for Previously Treated Unresectable, Locally Advanced or Metastatic Cholangiocarcinoma.” Regulatory approval announcement. 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.
