Overview
11 DESCRIPTION Futibatinib is a kinase inhibitor with the chemical name 1-[(3 S )-3-{4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]- 1 H -pyrazolo[3,4- d ]pyrimidin-1-yl}pyrrolidin-1-yl]prop-2-en-1-one. Futibatinib has a molecular formula of C 22 H 22 N 6 O 3 and molecular mass of 418.45 g/mole. Futibatinib has the following chemical structure: Futibatinib is a white crystalline powder.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics Serum Phosphate Futibatinib increased serum phosphate levels due to FGFR inhibition.
Indications
- 1 INDICATIONS AND USAGE 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 [see Dosage and Administration (2.1) ] . This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.1) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Common Doses
- 20 mg
- 4 mg
- 16 mg
- 12 mg
Dosage
2 DOSAGE AND ADMINISTRATION Confirm the presence of an FGFR2 gene fusion or other rearrangement prior to initiation of treatment with LYTGOBI. ( 2.1 ) Recommended dose is 20 mg orally (five 4 mg tablets or one 16 mg tablet and one 4 mg tablet) once daily until disease progression or unacceptable toxicity occurs. ( 2.2 ) Swallow tablet whole, with or without food. ( 2.2 ) 2.1 Patient Selection Select patients for the treatment of unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma with LYTGOBI based on the presence of an FGFR2 gene fusion or rearrangement [see Clinical...
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Ocular Toxicity [see Warnings and Precautions (5.1) ] Hyperphosphatemia and Soft Tissue Mineralization [see Warnings and Precautions (5.2) ] 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. ( 6.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A inhibitors : Avoid concomitant use. ( 7.1 ) Strong CYP3A inducers : Avoid concomitant use. ( 7.1 ) 7.1 Effect of Other Drugs on LYTGOBI Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors with LYTGOBI. Futibatinib is a CYP3A substrate [see Clinical Pharmacology (12.3) ] . Concomitant use of a strong CYP3A inhibitor increases futibatinib exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions. Strong CYP3A Inducers Avoid concomitant use of strong CYP3A inducers with LYTGOBI.