A phase I, dose-escalation study of the novel Polo-like kinase inhibitor volasertib (BI 6727) in patients with advanced solid tumours

Eur J Cancer. 2012 Jan;48(2):179-86. doi: 10.1016/j.ejca.2011.11.001. Epub 2011 Nov 24.


Background: Volasertib (BI 6727) is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase (Plk). This phase I dose-escalation study evaluated the maximum tolerated dose (MTD) of volasertib, safety and efficacy, and pharmacokinetic (PK) parameters.

Methods: This trial followed an open-label, toxicity-guided dose-titration design. Patients with progressive advanced or metastatic solid tumours received a single 1-h infusion of volasertib every 3 weeks. A total of 65 patients were treated at doses of 12-450 mg.

Results: Reversible haematological toxicity was the main side-effect; thrombocytopenia, neutropenia, and febrile neutropenia constituting the main dose-limiting events. Anaemia (all grades 22%; grade 3: 8%), neutropenia (15%; grade 3/4: 14%), fatigue (15%; grade 3: 2%), and thrombocytopenia (14%; grade 3/4: 14%) were the most frequent drug-related adverse events. The MTD was 400mg; however, 300 mg was the recommended dose for further development based on overall tolerability. Three patients achieved confirmed partial response. Stable disease as best response was reported in 40% of patients. Two patients remained progression free for >1 year. PK analysis showed no indication of deviation from 'dose-linear PK' behaviour, a large volume of distribution (>4000 l), moderate clearance and a long half-life (~111 h).

Conclusion: This first-in-man trial demonstrated a favourable PK profile of volasertib, with manageable toxicities. As expected, the most common events were haematological. Encouraging preliminary antitumour activity has been observed, supporting Plk inhibition as a therapeutic approach. Clinical development of volasertib in phase II monotherapy and combination trials is ongoing.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pteridines / pharmacokinetics
  • Pteridines / therapeutic use*
  • Young Adult


  • Antineoplastic Agents
  • BI 6727
  • Protein Kinase Inhibitors
  • Pteridines