Volasertib is a potent inhibitor of Polo-like kinase (PLK) 1 and to lesser extent also PLK2 and PLK3. PLKs are key regulators of the cell cycle and volasertib blocks cells in G2-M phase of the cell cycle. The compound has been evaluated in Phase I and II studies in acute myeloid leukemia and solid tumors. Side effects are mainly hematological. In acute myeloid leukemia (AML), a randomized Phase II study has been conducted in elderly patients unfit for intensive chemotherapy. Patients have been randomized to a combination of volarsetib and low-dose cytarabine versus low-dose cytarabine alone. Preliminary results show significantly higher rates of complete remission and of complete remission with incomplete hematological recovery in the combination versus the monotherapy arm, with 31% and 13%, respectively. Longer event-free survival was observed with the combination with 5.6 versus 2.3 months, respectively (p = 0.0237). These encouraging data supported the initiation of an international Phase III trial, which currently underway, to confirm these results. Volasertib has not yet been approved for regular clinical use.
