The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: A phase I, open-label, single dose-escalation study

Julie M. Vose, Jonathan W. Friedberg, Edmund K. Waller, Bruce D. Cheson, Vasthala Juvvigunta, Holger Fritsch, Claude Petit, Gerd Munzert, Anas Younes

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Polo-like kinase 1 (Plk1) is expressed during mitosis and overexpressed in multiple cancers, including non-Hodgkin lymphoma (NHL). This phase I study determined the maximum tolerated dose (MTD) of BI 2536, a Plk1 inhibitor, as a 1 h infusion once every 3 weeks in post-transplant relapsed (n = 17) and transplant-naive (n = 24) patients with relapsed/refractory NHL. Median treatment cycles were 2 and 1.5, respectively. MTD was 175 mg for both populations; dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia. Most treatment-related adverse events were grade 1/2; drug-related grade 3/4 events included thrombocytopenia and neutropenia. Four patients achieved responses (three complete and one partial at doses ≥ 150 mg, all post-transplant relapsed patients) for an overall response rate of 9.8%. BI 2536 exhibited multi-compartmental pharmacokinetics with a high volume of distribution. The activity and safety of BI 2536 in this pretreated patient population support Plk inhibitors as a therapeutic strategy in oncology.

Original languageEnglish (US)
Pages (from-to)708-713
Number of pages6
JournalLeukemia and Lymphoma
Volume54
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • BI 2536
  • Non-Hodgkin lymphoma
  • Single dose-escalation study

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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