Phase I Study of the Aurora B Kinase Inhibitor Barasertib (AZD1152) to Assess the Pharmacokinetics, Metabolism and Excretion in Patients With Acute Myeloid Leukemia

Cancer Chemother Pharmacol. 2012 Sep;70(3):461-9. doi: 10.1007/s00280-012-1939-2. Epub 2012 Aug 4.


Purpose: Barasertib (AZD1152) is a pro-drug that rapidly undergoes phosphatase-mediated cleavage in serum to release barasertib-hQPA, a selective Aurora B kinase inhibitor that has shown preliminary activity in clinical studies of patients with acute myeloid leukemia (AML). The pharmacokinetic (PK), metabolic and excretion profiles of barasertib and barasertib-hQPA were characterized in this open-label Phase I study.

Methods: Five patients with poor prognosis AML (newly diagnosed, relapsed or refractory) received barasertib 1,200 mg as a 7-day continuous infusion every 28 days. On Day 2 of Cycle 1 only, patients also received a 2-hour infusion of [(14)C]-barasertib. Blood, urine and feces samples were collected at various time points during Cycle 1. Safety and preliminary efficacy were also assessed.

Results: Barasertib-hQPA was extensively distributed to tissues, with a slow rate of total clearance (CL = 31.4 L/h). Overall, 72-82 % of radioactivity was recovered, with approximately double the amount recovered in feces (mean = 51 %) compared with urine (mean = 27 %). The main metabolism pathways for barasertib were (1) cleavage of the phosphate group to form barasertib-hQPA, followed by oxidation and (2) loss of the fluoroaniline moiety to form barasertib-hQPA desfluoroaniline, followed by oxidation. One of the four patients evaluable for response entered complete remission. No new or unexpected safety findings were observed; the most common adverse events were nausea and stomatitis.

Conclusions: The PK profile of barasertib is similar to previous studies using the same dosing regimen in patients with AML. The majority of barasertib-hQPA clearance occurred via hepatic metabolic routes.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aurora Kinase B
  • Aurora Kinases
  • Female
  • Humans
  • Infusions, Intravenous
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Organophosphates / adverse effects
  • Organophosphates / pharmacokinetics*
  • Organophosphates / therapeutic use
  • Prodrugs
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics*
  • Quinazolines / therapeutic use
  • Remission Induction
  • Time Factors
  • Treatment Outcome


  • 2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate
  • Organophosphates
  • Prodrugs
  • Quinazolines
  • AZD 1152-HQPA
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases