On May 28, 2021, the FDA accelerated the approval of infigratinib (Truseltiq; QED Therapeutics), an oral kinase inhibitor, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) and FGFR2 fusion or other rearrangement, as detected by an FDA-approved test.
The FDA granted infigratinib priority and fast-track review, as well as orphan drug designation for this indication. Infigratinib is the second targeted therapy approved by the FDA for this patient population.
On the same day, the FDA approved the FoundationOne CDx test as a companion diagnostic to infigratinib for selecting patients with CCA and FGFR2 fusion or other rearrangement for infigratinib treatment.
The approval of infigratinib was based on results from CBGJ398X2204, a multicenter, open-label, single-arm clinical trial of 108 patients with previously treated, unresectable locally advanced or metastatic CCA and an FGFR2 fusion or rearrangement. Patients received infigratinib 125 mg once daily for 21 days, followed by 7 days off, in 28-day cycles, until disease progression or unacceptable side effects.
The primary end points were overall response rate(ORR) and duration of response (DOR). The ORR was 23% (95% confidence interval [CI], 16-32), including 1 complete response and 24 partial responses. The median DOR was 5 months (95% CI, 3.7-9.3). Among the 23 patients who responded to therapy, the DOR was ≥6 months in 8 patients.
The most common (≥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. Grade 3 or 4 adverse events included hyperphosphatemia and retinal pigment epithelial detachment.
Continued approval for this indication may be contingent on clinical benefit in confirmatory trial(s).