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

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.

Keywords::

• BI 2536
• single dose-escalation study
• non-Hodgkin lymphoma

Acknowledgements

The authors would like to acknowledge GeoMed for editorial assistance with this manuscript.

The authors would like to acknowledge the contributions of the bioanalytical laboratory of Martina Wein (Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany).

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

The study was funded by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Victoria A. Robb, of GeoMed, during the preparation of this manuscript.