Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer

Expert Opin Investig Drugs. 2020 Aug;29(8):779-792. doi: 10.1080/13543784.2020.1783238. Epub 2020 Jun 25.


Introduction Patients with high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and current chemotherapy regimens for treating advanced disease are far from satisfactory. Prexasertib (LY2606368) is a novel checkpoint kinase inhibitor (CHK) under investigation for the treatment of HGSOC. Data from a recent phase II trial showed promising efficacy and safety results for treating wild-type BRCA HGSOC. Areas covered This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to the preclinical evidence of a synergic action.

Keywords: CHK inhibitors; Checkpoint kinase 1; LY2606368; PARP inhibitors; checkpoint kinase 2; high-grade serous ovarian cancer; homologous recombination; olaparib; prexasertib.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / pathology
  • Drug Synergism
  • Female
  • Humans
  • Neoplasm Grading
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazines / administration & dosage*
  • Pyrazines / adverse effects
  • Pyrazines / pharmacology
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacology


  • Protein Kinase Inhibitors
  • Pyrazines
  • Pyrazoles
  • prexasertib