The Food and Drug Administration (FDA) has granted accelerated approval to Truseltiq™ (infigratinib) for the treatment of 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.
Truseltiq is an orally administered, ATP-competitive, tyrosine kinase inhibitor of FGFR. The approval was based on data from a multicenter, single-arm phase 2 study (ClinicalTrials.gov Identifier: NCT02150967) that evaluated the efficacy and safety of infigratinib in 108 patients.
Study participants received infigratinib 125mg orally once daily for 21 consecutive days followed by 7 days off therapy for a 28-day cycle until disease progression or unacceptable toxicity. The main outcome measures were overall response rate (ORR) and duration of response (DOR), according to RECIST v1.1.
Results showed an ORR of 23% (95% CI, 16-32), with 1% (n=1) of patients achieving complete response and 22% (n=24) having partial response. The median DOR was 5 months (95% CI, 3.7-9.3); 32% (n=8) of responders had a response duration of at least 6 months and 4% (n=1) had a response duration of at least 12 months. The median time to response was 3.6 months (range, 1.4-7.4 months).
As for safety, the most common adverse reactions were 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, vomiting, and laboratory abnormalities.
Treatment with Truseltiq is associated with a risk of ocular toxicity including retinal pigment epithelial detachment. It may also cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, nonuremic calciphylaxis, vascular calcification, and myocardial calcification.
Truseltiq will be supplied as 25mg and 100mg capsules in 21-day blister cards.
The FDA has 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.
- BridgeBio Pharma’s affiliate QED Therapeutics and Partner Helsinn Group announce FDA approval of Truseltiq™ (infigratinib) for patients with cholangiocarcinoma. [press release]. Palo Alto, CA and Lugano, Switzerland: BridgeBio Pharma, Inc. and Helsinn Group; May 28, 2021.
- Truseltiq [package insert]. Brisbane, CA: QED Therapeutics, Inc.; 2021.