The US Food and Drug Administration (FDA) has granted accelerated approval to Lytgobi® (futibatinib) for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangements.

Lytgobi is an oral, selective, and irreversible small-molecule kinase inhibitor of FGFR1/2/3/4. It covalently binds to FGFR2, inhibiting the signaling pathway and decreasing cell viability in cancer cell lines with FGFR alterations.

The approval of Lytgobi was based on data from the open-label, single-arm phase 2b TAS-120-101 trial (ClinicalTrials.gov Identifier: NCT02052778). The trial was designed to evaluate futibatinib in 103 adults with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene rearrangements, including fusions. Patients received futibatinib at 20 mg orally once daily until disease progression or unacceptable toxicity.


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Results showed an overall response rate of 42% (primary endpoint; [95% CI, 32-52]); all 43 responders had a partial response. The median duration of response (secondary endpoint) was 9.7 months (95% CI, 7.6-17.1); 72% (n=31) of responders had responses lasting at least 6 months, while 14% (n=6) had responses lasting at least 12 months. The median time to response was 2.5 months (range, 0.7-7.4 months). Under the accelerated approval pathway, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The most common adverse reactions reported 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. 

Treatment with Lytgobi is associated with a risk of retinal pigment epithelial detachment. It may also cause hyperphosphatemia leading to soft tissue mineralization, as well as fetal harm.

Lytgobi is supplied as 4 mg tablets of futibatinib packaged in 7-day blister cards to provide 12 mg, 16 mg, or 20 mg daily doses. Patients should be selected for treatment based on the presence of an FGFR2 gene fusion or rearrangement.

References

  1. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. News release. US Food and Drug Administration. September 30, 2022. Accessed October 3, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-futibatinib-cholangiocarcinoma
  2. FDA approves Taiho’s Lytgobi® (futibatinib) tablets for previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma. News release. Taiho Oncology, Inc. September 30, 2022. Accessed October 3, 2022. https://www.prnewswire.com/news-releases/fda-approves-taihos-lytgobi-futibatinib-tablets-for-previously-treated-unresectable-locally-advanced-or-metastatic-intrahepatic-cholangiocarcinoma-301638254.html
  3. Lytgobi. Package insert. Taiho Oncology, Inc.; 2022. Accessed October 3, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214801s000lbl.pdf

This article originally appeared on MPR