[Pharmacological characteristics and clinical study results of Pemigatinib (Pemazyre® Tablets), a selective fibroblast growth factor receptor (FGFR) inhibitor].

ABSTRACT

Pemigatinib (Pemazyre® Tablets 4.5 mg) is a novel fibroblast growth factor receptor (FGFR) inhibitor, created by Incyte Corporation. The product was approved in March 2021 and was launched in June 2021 for the treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that has progressed after at least one prior line of systemic therapy. Pemigatinib was shown to selectively inhibit kinase activity of FGFR1～3 (IC50; 0.39～1.2 nM). In cultured cells, pemigatinib inhibited the phosphorylation of FGFR1 and its downstream signals, ERK1/2 and STAT5 in a concentration-dependent manner. Pemigatinib also potently inhibited the growth of various types of cell lines with FGFR 1～3 gene alteration. Pemigatinib was shown to induce concentration-dependent tumor regression in a tumor xenograft model mice in which tumor tissue sections from patients with cholangiocarcinoma (CCA) harboring FGFR2 gene fusions were transplanted. Pemigatinib was well tolerated in Japanese and overseas Phase1 studies (INCB 54828-101 and 202). In the global phase2 study (INCB 54828-202) conducted in CCA patients with FGFR2 gene fusions or rearrangements, significant improvement in the overall response rate was observed. Although several adverse reactions were observed which was based on the mechanism of action of pemigatinib, the safety profile and management of the adverse reactions were favorable. Pemigatinib is expected to contribute to second-line drug treatment after failure of standard therapies in biliary tract cancer.