Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Volasertib induces mitotic arrest and apoptosis by targeting Polo‐like kinases. In this phase I dose‐escalation study, the maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of volasertib were determined in pediatric patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients aged 2 to <18 years with relapsed/refractory acute leukemia/advanced solid tumors (ST) without available effective treatments were enrolled—cohort C1 (aged 2 to <12 years); cohort C2 (aged 12 to <18 years). The patients received volasertib intravenously (starting dose: 200 mg/m<jats:sup>2</jats:sup> body surface area on day 1, every 14 days). The primary endpoint was the pediatric MTD for further development.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twenty‐two patients received treatment (C1: leukemia, n = 4; ST, n = 8; C2: leukemia, n = 3; ST, n = 7). No dose‐limiting toxicities (DLTs) occurred up to 300 mg/m<jats:sup>2</jats:sup> volasertib in C1; two patients in C2, at 250 mg/m<jats:sup>2</jats:sup> volasertib, had DLTs in cycle 1, one of which led to death; therefore, the MTD of volasertib in C2 was 200 mg/m<jats:sup>2</jats:sup>. The most common grade 3/4 adverse events (all patients) were febrile neutropenia, thrombocytopenia, and neutropenia (41% each). Stable disease (SD) was the best objective response (leukemia, n = 5; ST, n = 2); the duration of SD was short in all patients, except in one with an ST. PK profiles were generally comparable across dose groups and were consistent with those in adults.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The pediatric MTD/dose for further development was identified. There were no unexpected safety or PK findings; limited antitumor/antileukemic activity was demonstrated.</jats:p></jats:sec>