Futibatinib

LYTGOBI is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). LYTGOBI is a kinase inhibitor indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.

Futibatinib is a small molecule kinase inhibitor of FGFR 1, 2, 3, and 4 with IC 50 values of less than 4 nM. Futibatinib covalently binds FGFR. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Futibatinib inhibited FGFR phosphorylation and downstream signaling and decreased cell viability in cancer cell lines with FGFR alterations including FGFR fusions/rearrangements, amplifications, and mutations. Futibatinib demonstrated anti-tumor activity in mouse and rat xenograft models of human tumors with activating FGFR genetic alterations.

Confirm the presence of an FGFR2 gene fusion or other rearrangement prior to initiation of treatment with LYTGOBI. Recommended dose is 20 mg orally once daily until disease progression or unacceptable toxicity occurs. Swallow tablet whole, with or without food.

None. None

Ocular Toxicity: LYTGOBI can cause retinal pigment epithelial detachment (RPED). Perform a comprehensive ophthalmological examination including optical coherence tomography (OCT) prior to initiation of therapy, every 2 months for the first 6 months, and every 3 months thereafter and urgently at any time for visual symptoms. Hyperphosphatemia and Soft Tissue Mineralization: Increases in phosphate levels can cause hyperphosphatemia leading to soft tissue mineralization, calcinosis, nonuremic calciphylaxis and vascular calcification. Monitor for hyperphosphatemia and withhold, reduce the dose, or permanently discontinue based on duration and severity of hyperphosphatemia. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception.

The following adverse reactions are discussed elsewhere in the labeling: Ocular Toxicity Hyperphosphatemia and Soft Tissue Mineralization Most common (≥20%) adverse reactions 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.

Strong CYP3A inhibitors: Avoid concomitant use. Strong CYP3A inducers: Avoid concomitant use. Effect of Other Drugs on LYTGOBI Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors with LYTGOBI. Futibatinib is a CYP3A substrate. Concomitant use of a strong CYP3A inhibitor increases futibatinib exposure, which may increase the risk of adverse reactions. Strong CYP3A Inducers Avoid concomitant use of strong CYP3A inducers with LYTGOBI. Concomitant use of a strong CYP3A inducer decreases futibatinib exposure, which may reduce the effectiveness of LYTGOBI.

Store LYTGOBI tablets at room temperature 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F). ().