The US Food and Drug Administration (FDA) has approved lirafugratinib (Lyrfigtu, Elevar Therapeutics, Inc.), a kinase inhibitor, 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.

Efficacy was evaluated in REFOCUS (NCT04526106), a multicenter, open-label, single-arm trial in 116 patients with unresectable or metastatic cholangiocarcinoma who were naïve to FGFR inhibitor treatment and had received prior chemotherapy or chemoimmunotherapy. Patients received lirafugratinib 70 mg once daily until disease progression or unacceptable toxicity.

The major efficacy outcome measures were Objective Response Rate (ORR) and Duration of Response (DOR) as determined by an independent review committee according to RECIST v1.1. ORR was 46 percent (95 percent CI: 36, 55) and median DOR was 11.8 months (95 percent CI: 7.5, 13.0).

The prescribing information includes warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralisation, and embryo-fetal toxicity.

The recommended lirafugratinib dose is 70 mg orally once daily until disease progression or unacceptable toxicity.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted Priority Review (PR). Lirafugratinib received Breakthrough Therapy and Orphan Drug designations.