On September 30, the U.S. Food and Drug Administration (FDA) granted accelerated approval to futibatinib (Lytgobi) for adults with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.
Efficacy was evaluated in TAS-120-101 (ClinicalTrials.gov identifier NCT02052778), a multicenter, open-label, single-arm trial that enrolled 103 patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma and an FGFR2 gene fusion or other rearrangement. The presence of FGFR2 fusions or other rearrangements was determined using next-generation sequencing testing. Patients received 20 mg of futibatinib orally once daily until disease progression or unacceptable toxicity.
The major efficacy outcome measures were overall response rate and duration of response, as determined by an independent review committee according to Response Evaluation Criteria in Solid Tumors version 1.1. Overall response rate was 42% (95% confidence Interval [CI] = 32%–52%); all 43 responders achieved partial responses. The median duration of response was 9.7 months (95% CI = 7.6–17.1 months).
The most common adverse reactions occurring in 20% or more of patients treated with futibatinib were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.
The recommended futibatinib dose is 20 mg orally once daily until disease progression or unacceptable toxicity occurs.
This review used the Real-Time Oncology Review 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.
The application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.