On May 16, the U.S. Food and Drug Administration (FDA) announced the final withdrawal of the approval of infigratinib (Truseltiq) for previously treated patients with unresectable, locally advanced, or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement.
The accelerated approval of infigratinib—granted in May 2021—required the sponsor to conduct postmarketing trials to verify the clinical benefit of the drug. The sponsor voluntarily requested withdrawal of infigratinib. The sponsor’s request cited difficulties in recruiting and enrolling study subjects for the required confirmatory clinical trial in first-line treatment of cholangiocarcinoma (a new indication under investigation for infigratinib), and the determination that, as a result, continued distribution of infigratinib in the second-line treatment of cholangiocarcinoma (the accelerated approval indication) was not commercially reasonable.
Accelerated Approval
Infigratinib’s May 2021 accelerated approval was granted on the basis of data from the phase II CBGJ398X2204 study (ClinicalTrials.gov identifier NCT02150967). 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.
