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Jump to Key Points The FDA has approved lirafugratinib (Lyrfigtu, Elevar Therapeutics) for adults with previously treated unresectable, locally advanced, or metastatic cholangiocarcinoma harboring a fibroblast growth factor receptor 2 (FGFR2) gene fusion or other rearrangement.
The FGFR2-targeted tyrosine kinase inhibitor joins two others already on the US market: pemigatinib and futibatinib. Pemigatinib carries the same second-line indication while futibatinib’s indication is limited to intrahepatic disease.
In a press release, the drug’s maker, Elevar, said lirafugratinib “selectively targets FGFR2, differentiating it from existing pan-FGFR inhibitors that broadly inhibit FGFR1, FGFR3, and/or FGFR4 in addition to FGFR2. Consistent with its high selectivity, the rates of hyperphosphatemia and diarrhea – adverse events commonly associated with non-selective FGFR inhibitors – were 20.7% and 21.6%, respectively,” in testing.
Approval was based on the single-arm phase 1/2 ReFocus trial in 116 patients new to FGFR2 blockers after prior chemotherapy or chemoimmunotherapy.
- FDA approved lirafugratinib for previously treated FGFR2-rearranged cholangiocarcinoma.
- Indication: unresectable, locally advanced, or metastatic disease in adults.
- Approval based on phase 1/2 ReFocus; ORR 46%, median DOR 11.8 months.
- Median PFS 11.3 months; median OS 22.8 months in trial population.
- Common AEs: nail toxicity, PPE, stomatitis, alopecia; ocular toxicity and hyperphosphatemia warnings.
Forty-six percent of patients had an objective response with a median duration of response of 11.8 months. Median progression-free survival was 11.3 months and median overall survival was 22.8 months, according to the Elevar press release.
Across 385 patients who have received lirafugratinib, the most common adverse events in 20% or more were nail toxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, alopecia, dry eye, dry mouth, fatigue, dysgeusia, retinal pigment epithelial detachment, constipation, dry skin, infection, rash, abdominal pain, hemorrhage, blurred vision, diarrhea, musculoskeletal pain, nausea, and decreased appetite.
Almost a third had serious adverse reactions, including infection (6%), pneumonia (3.4%), fatigue (2.6%), and hemorrhage (2.6%), which was fatal in one patient.
Like its competitors, lirafugratinib labeling carries warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.
The recommended dose is 70 mg orally once daily until disease progression or unacceptable toxicity.
Elevar expects to launch the drug in the fourth quarter of 2026.
M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net
