On 1st August 2018, the European Medicines Agency’s (EMAs) Committee for Orphan Medicinal Products (COMP) granted a positive opinion recommending PCM-075, a polo-like kinase 1 (PLK1) inhibitor, for designation as an orphan medicinal product for the treatment of acute myeloid leukemia (AML).1
PLK1 is expressed at very low levels in most normal tissues. However, it has been found to be overexpressed in multiple AML cell lines and also in leukemia blasts from patients with AML. Overexpression of PLK1 in patients with AML has been reported to be associated with poor prognosis in these group of patients.2 PCM-075 is an oral, highly selective adenosine triphosphate (ATP) competitive inhibitor, which inhibits the PLK1 enzyme, thereby inducing cell cycle arrest and apoptosis in cancer cells.3
At present, PCM-075 is being evaluated in a phase Ib/II study (NCT03303339), which is evaluating the safety and efficacy of PCM-075 in combination with decitabine or low-dose cytarabine in adult patients with AML, who are relapsed or refractory. The primary objectives of the phase Ib portion of the study were the number of patients with dose-limiting toxicities and adverse events. The primary objective of the phase II portion of the study is the rate of complete response (CR) plus CR with incomplete blood count recovery (CRi).