General Description

Lytgobi (futibatinib) is a kinase inhibitor.

Lytgobi is specifically 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.

Lytgobi is supplied as tablets for oral administration. 

• The recommended dosage of Lytgobi is 20 mg (five 4 mg tablets) taken orally once daily until disease progression or unacceptable toxicity occurs.
• Take Lytgobi with or without food at approximately the same time each day. Swallow tablets whole. Do not crush, chew, split, or dissolve tablets.
• If the patient misses a dose of Lytgobi for more than 12 hours or if vomiting occurs, resume dosing with the next scheduled dose.

Mechanism of Action

Lytgobi (futibatinib) is a small molecule kinase inhibitor of FGFR 1, 2, 3, and 4. 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.

Side Effects

Adverse effects associated with the use of Lytgobi (futibatinib) may inlcude, but are not limited to, the following:

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, vomiting and certain lab abnormalities

Clinical Trial Results

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.

The FDA approval of Lytgobi (futibatinib) was based on the results of the primary analysis of the FOENIX-CCA2 trial, a global Phase 2 open-label trial evaluating 103 patients with unresectable, locally advanced or metastatic iCCA harboring FGFR2 gene rearrangements including fusions. In this trial, patients received Lytgobi orally once daily at a dose of 20mg until disease progression or unacceptable toxicity. The trial met its primary endpoint with an objective response rate of 42%. The median duration of response (DOR) was 9.7 months, with 72% of responses lasting at least six months.