Infigratinib (BGJ398): an investigational agent for the treatment of FGFR-altered intrahepatic cholangiocarcinoma

Expert Opin Investig Drugs. 2021 Apr;30(4):309-316. doi: 10.1080/13543784.2021.1864320. Epub 2021 Jan 4.

Abstract

Introduction: The fibroblast growth factor receptor (FGFR) pathway is essential in cell proliferation, differentiation, migration, and survival. Cancers such as intrahepatic cholangiocarcinoma (IHCA) have demonstrated alterations of FGFR allowing unregulated growth. Infigratinib (BGJ398) is a potent ATP-competitive inhibitor of all four FGFR receptors as demonstrated by the consistently high prevalence of hyperphosphatemia, indicating disruption of FGFR-related phosphate homeostasis.

Areas covered: In this article, the authors discuss preclinical studies and the biological characterization of BGJ398 that inspired its investigation for cancer treatment. They summarize results from phase I and II studies and comment on ongoing phase III clinical trials primarily focusing on its role in treating IHCA.

Expert opinion: Infigratinib exhibits high potency FGFR1-3 inhibition in preclinical studies. Clinically, agents targeting FGFR including infigratinib show promising anti-tumor activity in targeted trials. Pemigatinib, an FGFR inhibitor, has recently been approved by the FDA for use in refractory IHCA. We believe infigratinib represents a promising agent in the treatment of refractory IHCA with FGFR2 fusions and is uniquely positioned to be a potential option in chemonaive patient populations. An ongoing phase III trial (PROOF-301) compares the efficacy and safety of infigratinib versus standard gemcitabine and cisplatin in untreated patients with IHCA and FGFR2 fusions.

Keywords: Cholangiocarcinoma; bgj398; chemotherapy; fgfr; infigratinib.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / pathology
  • Humans
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacology
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyrimidines
  • Receptors, Fibroblast Growth Factor
  • infigratinib