On May 28, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement, as detected by an FDA-approved test.
The FDA also approved FoundationOne CDx (Foundation Medicine, Inc.) for selection of patients with FGFR2 fusion or other rearrangement as a companion diagnostic device for treatment with infigratinib.
Efficacy was demonstrated in CBGJ398X2204 (ClinicalTrials.gov identifier NCT02150967), a multicenter, open-label, single-arm trial that enrolled 108 patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement as determined by local or central testing. Patients received infigratinib at 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy in 28-day cycles until disease progression or unacceptable toxicity.
The major efficacy outcome measures were overall response rate and duration of response as determined by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1.
The overall response rate was 23% (95% confidence interval [CI] = 16%–32%), with 1 complete response and 24 partial responses. Median duration of response was 5 months (95% CI = 3.7–9.3). Among the 23 responders, 8 patients maintained the response for 6 months or more.
The most common (incidence ≥ 20%) adverse reactions were hyperphosphatemia, increased creatinine, nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting. Serious risks associated with infigratinib treatment include hyperphosphatemia and retinal pigment epithelial detachment; monitoring for these adverse reactions during treatment is recommended.
The recommended infigratinib dose is 125 mg orally once daily on an empty stomach for 21 consecutive days followed by 7 days off therapy in 28-day cycles.
This indication is approved under accelerated approval based on the overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada. The application reviews are ongoing at the other regulatory agencies.
This application was granted Priority Review, Fast Track Designation, and Orphan Drug Designation.