Futibatinib Wins Accelerated FDA Approval in Cholangiocarcinoma

FDA on Friday granted accelerated approval for futibatinib for patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma, when they have gene fusions or rearrangements in the fibroblast growth factor receptor 2 (FGFR2).

The targeted therapy, to be sold by Taiho Oncology as Lytgobi, had previously received breakthrough status in 2021 and was accepted for priority review in March.

Cholangiocarcinomas, which are cancers of the bile ducts, are relatively rare and challenging to treat, but investigators have made advances recently in part by exploiting genetic alterations that are abundant in these cancers. About 20% of those diagnosed have intrahepatic disease, meaning tumors are found inside the liver; of these patients, 10% to 16% have FGFR2 gene arrangements that promote tumor growth.

Futibatinib’s approval follows results from FOENIX-CCA2, a phase 2b trial that tested the drug in 103 patients with the FGFR2 alteration; when patients took the 20-mg tablet daily, the overall response rate was 42%, and the median duration of response was 9.7 months, with 72% of responses lasting at least 6 months. Ongoing approval may be contingent on results from a confirmatory trial.

“This approval is an important milestone for patients and may provide hope for improved outcomes. As someone whose family has been impacted by cholangiocarcinoma, I’m acutely aware of the impact this disease can have on the patient and their loved ones,” said Tim Whitten, president and CEO, Taiho Oncology, in a statement.

Futibatinib works by covalently binding to FGFR2 and inhibiting the signaling pathway, making it an example of precision medicine in intrahepatic cholangiocarcinoma, according to medical oncologist Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center and lead investigator of FOENIX-CCA2 trial. “I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years,” she said.

The most common adverse reactions were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, dry skin, arthralgia, dysgeusia, abdominal pain, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.