Volasertib (BI 6727): A Comprehensive Profile of a Polo-Like Kinase 1 Inhibitor from Clinical Promise to Precision-Guided Revival

Executive Summary

Volasertib (BI 6727) is an investigational, first-in-class, small-molecule inhibitor of Polo-like kinase 1 (PLK1), a critical regulator of mitosis. Developed by Boehringer Ingelheim, the compound demonstrated high potency against its target, inducing a characteristic "Polo arrest" that leads to cell cycle disruption and apoptosis, preferentially in malignant cells. Preclinical data showed broad antitumor activity across a range of solid and hematological malignancies, with the strongest rationale emerging for the treatment of acute myeloid leukemia (AML).

The clinical development of volasertib was characterized by a trajectory of significant promise followed by a profound setback. A randomized Phase II study in elderly AML patients unfit for intensive chemotherapy showed that the combination of volasertib with low-dose cytarabine (LDAC) more than doubled the objective response rate and significantly improved both event-free and overall survival compared to LDAC alone. These compelling results led to the U.S. Food and Drug Administration (FDA) granting Breakthrough Therapy and Orphan Drug designations and prompted the initiation of a large, pivotal Phase III trial, POLO-AML-2.