UPDATE: On May 16, 2024, the U.S. Food and Drug Administration (FDA) announced final withdrawal of its accelerated approval of infigratinib (Truseltiq™) for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement.

The accelerated approval required the sponsor to conduct postmarketing trials to verify the clinical benefit of the drug. The sponsor voluntarily requested the withdrawal, citing difficulties in recruiting and enrolling participants for the required confirmatory clinical trial in first-line cholangiocarcinoma (a new indication under investigation for infigratinib), and the determination that, as a result, continued distribution of infigratinib in second-line cholangiocarcinoma (the accelerated approval indication) was not commercially reasonable.

On May 28, 2021, FDA granted accelerated approval to infigratinib (Truseltiq™), a kinase inhibitor for patients 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. FDA also approved the FoundationOne® CDx as a companion diagnostic for infigratinib. 

FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma

Efficacy was demonstrated in a multicenter, open-label, single-arm trial (CBGJ398X2204; NCT02150967), of 108 patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement. Patients received 28-day cycles of infigratinib 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy until they experienced disease progression or unacceptable toxicity.

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR), as determined by blinded independent central review according to response evaluation criteria in solid tumors 1.1. ORR was 23% (95% CI = 16, 32), with 1 complete response and 24 partial responses. Median DoR was five months (95% CI = 3.7, 9.3). Among the 23 responders, 8 patients maintained the response for six months or more. 

The most common adverse reactions (≥ 20%) were hyperphosphatemia, increased creatinine, nail toxicity, stomatitis, dry eyes, fatigue, alopecia, palmar-plantar erythrodysesthesia, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting. The serious risks included hyperphosphatemia and retinal pigment epithelial detachment.  

The recommended infigratinib dose is 28-day cycles of 125 mg orally once daily on an empty stomach for 21 consecutive days followed by 7 days off therapy. 

View the full prescribing information for infigratinib.

FDA approved the indication under accelerated approval based on ORR and DoR. Continued approval for the indication is contingent on verification and description of clinical benefit in confirmatory trials. 

The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada. The application reviews are ongoing at the other regulatory agencies. 

The review used the Real Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, as well as Assessment Aid and the Product Quality Assessment Aid, voluntary submissions from the applicant to facilitate FDA’s assessment. 

FDA granted the application priority review, fast-track designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov