CMML is a rare and aggressive hematologic malignancy that primarily affects older adults and is characterized by features of both myelodysplastic syndromes and myeloproliferative neoplasms. The disease is associated with poor clinical outcomes, including progressive bone marrow failure and the risk of transformation to acute myeloid leukemia (AML). Approximately one-third of patients with CMML harbor RAS mutations, which are associated with more aggressive disease and poorer outcomes. With limited treatment options available, there remains a significant need for new targeted therapies. By targeting PLK1, onvansertib has the potential to address a key pathway involved in RAS-driven cancers.

Onvansertib is currently being evaluated in an investigator-initiated Phase 1 clinical trial in patients with CMML. Early findings have supported the continued evaluation of PLK1 inhibition in this patient population and further reinforce the broader potential of onvansertib as a monotherapy in cancers with significant unmet medical need.