Pemiganitib. Fibroblast growth factor receptor inhibitor, Treatment of cholangiocarcinoma.

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis plays an important role in normal organ, vascular and skeletal development. Deregulation of FGFR signaling through genetic modification or overexpression of the receptors (or their ligands) has been observed in numerous tumor settings. Preclinical and clinical data showed that inhibition of FGFR signaling may result in antitumor effects, thus confirming the validity of the FGF/FGFR axis as a potential therapeutic target. Pemigatinib (INCB-054828), developed by Incyte Corporation, is an orally bioavailable inhibitor of FGFR types 1, 2 and 3 (FGFR-1/2/3) with antineoplastic activity. Pemigatinib is able to inhibit FGFR-1/2/3, which results in the inhibition of FGFR signaling pathways, thus causing an antiproliferative effect in FGFR-1/2/3- overexpressing tumor cells. The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program is currently assessing the efficacy and safety of pemigatinib in patients with several types of tumors. The drug candidate has been granted orphan drug designation for the treatment of cholangiocarcinoma both in the United States and Europe, and has also received breakthrough therapy designation in the United States for this indication. An update on the preclinical and clinical pharmacology of pemigatinib is provided in this review.