FDA Approves Lyrfigtu (Lirafugratinib) for Previously Treated FGFR2-Positive Bile Duct Cancer

FDA Approves Lyrfigtu (Lirafugratinib) for Previously Treated FGFR2-Positive Bile Duct Cancer

September 23–24, 2026. The FDA approved the oral FGFR2 inhibitor lirafugratinib (Lyrfigtu, Elevar Therapeutics) "for adults with previously treated cholangiocarcinoma (CCA) with FGFR2 fusion or other rearrangements" — unresectable, locally advanced, or metastatic disease. About 8,000 new U.S. cases of bile duct cancer are diagnosed each year (MedPage Today, citing the FDA's Wednesday announcement).

Principal support came from the Phase 1/2 ReFocus trial, in an analysis of 116 patients with previously treated FGFR2-positive CCA and no prior FGFR-inhibitor exposure:

• Objective response rate: 46%
• Median PFS: 11.3 months (49.2% 12-month PFS)
• Median overall survival: 22.8 months (74.6% 12-month OS)
• Disease control rate: 96.5%

The drug's differentiation is selectivity: "Lyrfigtu's unique, irreversible, covalent-binding mechanism enables potent and sustained inhibition of FGFR2, including many resistance mutations that can emerge with earlier FGFR inhibitors," said Lipika Goyal, MD, of Stanford Cancer Center, in Elevar's release. "Unlike earlier pan-FGFR inhibitors, it selectively targets FGFR2 while minimizing off-isoform toxicities."

Safety: the most common grade ≥3 treatment-related adverse events were palmar-plantar erythrodysesthesia (32.8%) and stomatitis (12.1%); the label includes warnings for ocular toxicity, hyperphosphatemia, soft tissue mineralization, and embryo-fetal toxicity. Elevar says lirafugratinib will be available in the U.S. before the end of the year.

Why it matters: cholangiocarcinoma has historically had limited options and poor outcomes; this adds a durable, FGFR2-selective targeted therapy for the FGFR2-fusion subset — and MSKCC's Alison Schram used the approval to press the broader point: "The results also reinforce the importance of molecular testing at diagnosis so that patients can be matched to therapies most likely to benefit them¹."