FDA Approves Infigratinib for Advanced/Metastatic Cholangiocarcinoma With FGFR2 Rearrangements


The FDA has granted accelerated approval to infigratinib (Truseltiq™, QED Therapeutics) for patients with previously treated unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement. In addition, the FDA approved the FoundationOne®CDx (Foundation Medicine, Inc.) companion diagnostic device for the detection of FGFR2 fusions/rearrangements in patients with cholangiocarcinoma.

“Treatment options for cholangiocarcinoma after progression on first-line gemcitabine-based therapy are limited,” wrote Milind M. Javle, MD, Professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, and colleagues, in their abstract of the CBGJ398X2204 clinical trial (NCT02150967), on which the approval was based. “A single-arm, phase 2 study evaluated infigratinib, an adenosine triphosphate (ATP)–competitive FGFR1-3–selective oral tyrosine kinase inhibitor, in previously-treated advanced cholangiocarcinoma with FGFR fusions/rearrangements.”

The multicenter open-label trial enrolled 108 patients with previously treated unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement. Patients received infigratinib 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 primary end point was overall response rate; the secondary end points were progression-free survival, disease control rate, overall survival, safety, and pharmacokinetics.

At a median follow-up of 10.6 months, infigratinib produced an overall response rate of 23% and a median duration of response of 5 months, with 8 of the 23 patients who responded experiencing a response lasting 6 months or longer. The median progression-free survival was 7.3 months.

The most common adverse reactions occurring in at least 20% of patients included 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 may include hyperphosphatemia and retinal pigment epithelial detachment; patients should be monitored for these toxicities during treatment.

“Infigratinib is associated with promising anticancer activity and a manageable adverse event profile in patients with advanced refractory cholangiocarcinoma with an FGFR2 fusion or rearrangement,” concluded Dr. Javle and colleagues in their January 2021 publication in the Journal of Clinical Oncology. “A phase 3 study of infigratinib versus gemcitabine/cisplatin is ongoing in the front-line setting.”

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

For More Information

Javle MM, Roychowdhury S, Kelly RK, et al (2021). Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol, 39(suppl_3):265-265. DOI:10.1200/JCO.2021.39.3_suppl.265

Clinicaltrials.gov (2020). A phase II, single arm study of BGJ398 in patients with advanced cholangiocarcinoma. NLM identifier: NCT02150967.

Truseltiq™ (infigratinib) prescribing information (2021). QED Therapeutics, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214622s000lbl.pdf

US Food & Drug Administration (2021). FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma

Image credit: Nephron. Licensed under CC BY-SA 3.0

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