Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial

Future Oncol. 2020 Oct;16(30):2375-2384. doi: 10.2217/fon-2020-0299. Epub 2020 Jun 25.

Abstract

Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain FGFR alterations. Infigratinib is an oral FGFR 1-3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic FGFR-altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with FGFR2 translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 (ClincalTrials.gov).

Keywords: cholangiocarcinoma; fibroblast growth factor receptor inhibitor; infigratinib; targeted therapy.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Cisplatin / administration & dosage
  • Clinical Protocols*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Oncogene Proteins, Fusion / genetics*
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • Receptor, Fibroblast Growth Factor, Type 2 / antagonists & inhibitors
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Research Design
  • Translocation, Genetic

Substances

  • Oncogene Proteins, Fusion
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Deoxycytidine
  • infigratinib
  • gemcitabine
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT03773302