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The FDA to futibatinib (Lytgobi) tablets for treating adults with intrahepatic cholangiocarcinomas that harbor fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.

Futibatinib, an oral drug that covalently binds to FGFR2 and inhibits the signaling pathway, is specifically indicated for patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma, an aggressive cancer of the bile ducts.

Support for the approval came from the phase II FOENIX trial, a multicenter, open-label study involving intrahepatic cholangiocarcinoma patients selected for FGFR2 rearrangements by next-generation sequencing. All 103 patients in the single-arm trial received a 20-mg daily dose of futibatinib until either disease progression or unacceptable toxicity.

Per independent review, the overall response rate (ORR) was 42% (95% CI 32-52) -- all of which were partial responses. Median duration of response was 9.7 months (95% CI 7.6-17.1), and 72% of the responses lasted 6 months or longer.

About 20% of cholangiocarcinomas are intrahepatic in nature. Of these, anywhere from 10-16% will have FGFR2 gene rearrangements, which promote tumor proliferation.

"Lytgobi is a key example of the potential of precision medicine in [intrahepatic cholangiocarcinomas] and represents another advance in the treatment of this rare and challenging disease," FOENIX investigator Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center in Boston, said in a from drugmaker Taiho Oncology.

Futibatinib is the third drug to be approved for intrahepatic cholangiocarcinoma related to FGFR2 gene fusions or rearrangements, following the accelerated approvals of pemigatinib (Pemazyre) and , both reversible ATP-competitive inhibitors.

Under the accelerated approval pathway, continued approval of futibatinib may be contingent on demonstration of clinical benefit in confirmatory trials.

In FOENIX, common (≥20%) adverse events with futibatinib included abdominal pain; alopecia; arthralgia; constipation; decreased appetite; diarrhea; dysgeusia; dryness of the eyes, skin, and mouth; fatigue; hand-foot syndrome; musculoskeletal pain; nail toxicity; nausea and vomiting; stomatitis; and urinary tract infections. Additionally, serious adverse events occurred in 39% of patients.

Warnings for the drug include the risk for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity. Lactating women should wait at least a week following the last dose of the drug before breastfeeding.

Due to the potential for drug interactions, concomitant use of futibatinib and dual P-glycoprotein and strong CYP3A inhibitors or inducers should be avoided, according to the drug's .

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