Folate receptor alpha antagonists in preclinical and early stage clinical development for the treatment of epithelial ovarian cancer

Expert Opin Investig Drugs. 2016 Dec;25(12):1405-1412. doi: 10.1080/13543784.2016.1254616.

Abstract

The prognosis of patients affected by ovarian cancer has not substantially changed in the last decades and improving survival still remains a challenge. In the promising era of 'personalized therapy' several new biologic therapies are currently being investigated: in this setting, targeting the folate receptor (FR) has been considered a new potential strategy for biologic therapy. Areas covered: The aim of the current review is to summarize, giving a critical overview,promising folate receptor alpha antagonists under preclinical or early clinical development for ovarian cancer. Expert opinion: Two categories of therapeutics are included in this class: FRα targeted mAbs and FRα-binding-ADC (Antibody drug conjugates); both share the interesting possibility of selecting patients via a biomarker which is already available. In the first class, farletuzumab has reached the most advanced stage in clinical evaluation and results of a Phase II randomized trial are awaited to assess its efficacy in a specific patients' setting. MOv18 IgE represents a novel strategy to target FRα expressing cells, which has shown encouraging results in preclinical studies: further evaluation is needed in the clinical setting. IMGN 853 is an innovative FRα-binding ADC under development, with only preliminary results of a Phase I trial available.

Keywords: Farletuzumab; folate receptor; folate-conjugates; ovarian cancer; target therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Ovarian Epithelial
  • Drug Design
  • Female
  • Folate Receptor 1 / antagonists & inhibitors*
  • Folate Receptor 1 / metabolism
  • Humans
  • Immunoconjugates / pharmacology
  • Immunoconjugates / therapeutic use
  • Maytansine / analogs & derivatives
  • Maytansine / pharmacology
  • Maytansine / therapeutic use
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Patient Selection
  • Prognosis
  • Randomized Controlled Trials as Topic

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Folate Receptor 1
  • Immunoconjugates
  • Maytansine
  • farletuzumab
  • mirvetuximab soravtansine