FDA Grants Priority Review to Infigratinib for the Treatment of Cholangiocarcinoma

The FDA has accepted a New Drug Application for the oral FGFR1-3 selective inhibitor, infigratinib (formerly BGJ398) and granted it Priority Review for the treatment of patients with cholangiocarcinoma, announced BridgeBio Pharma, Inc, in a press release.¹

The NDA for infigratinib will be evaluated through the FDA’s Real-Time Oncology Review pilot program and applications for approval will also be submitted in Canada and Australia under the Project Orbis Program.

Results from a phase 2, multicenter, single-arm study (NCT02150967) of infigratinib as third- or later-line treatment of patients with FGFR2 fusion–positive cholangiocarcinoma were most recently presented during the European Society of Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2020. The study showed that second-line chemotherapy, the most common second-line treatment approach for the disease, led to similar outcomes as front-line treatment in previously published studies, but clinical meaningful improvements in progression-free survival (PFS) and overall response rates (ORRs) were observed when the drug was administered as third-line treatment or later.²

A total of 71 patients were enrolled to the study and treated with infigratinib 125 mg orally once daily on days 1 through 21. Every 28 days, cycles of the agent were repeated until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent.

Three cohorts of patients were included in the study according to various FGFR genetic alterations. Patients had advanced or metastatic disease with FGFR2 gene fusions or translocations (cohort 1) or other FGFR genetic alterations who had progressed following treatment with a cisplatin/gemcitabine-containing regimen for advanced disease, or a prior FGFR inhibitor (cohort 3). The total patient population included 44 women and 27 men with a median age of 53 years. Overall, 37 of the patients enrolled were included a retrospective analysis which accesses ORR and PFS pe RECIST v1.1.

In the second-line setting, the median PFS observed with chemotherapy was 4.63 months (95% CI, 2.69-7.16) compared with 6.77 months (95% CI, 3.94-7.79) among patients treated with third- and later-line infigratinib.

In terms of ORRs, patients treated with second-line chemotherapy had an ORR of 5.4% (95% CI, 0.7%-18.2%) compared with 21.6% (95% CI, 9.8%-38.2%) for third- and later-line infigratinib.

The study of infigratinib in later-line settings for patients with FGFR2 fusion–positive cholangiocarcinoma is ongoing and recruiting patients. In addition to cholangiocarcinoma, infigratinib is being investigated as treatment of patients with urothelial carcinoma and achondroplasia whose tumors harbor FGFR mutations.¹

_References:

_{1. BridgeBio Pharma and Affiliate QED Therapeutics announce FDA acceptance of New Drug Application for infigratinib for the treatment of cholangiocarcinoma. News release. BridgeBio Pharma. December 1, 2020. Accessed December 1, 2020. https://bit.ly/36sxwZe}

_{2. Javle M, Sadeghi S, Roychowdhury S, et al. Efficacy of second-line chemotherapy in patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions: A retrospective analysis. Presented at: ESMO World Congress on Gastrointestinal Cancer 2020; July 1-4, 2020; Virtual. Abstract SO-5.}