Dr. Jabbour on the Rationale to Evaluate KO-539 in Relapsed/Refractory AML

Elias Jabbour, MD, a professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the rationale to evaluate KO-539 in relapsed/refractory acute myeloid leukemia (AML).

During the 2020 ASH Annual Meeting and Exposition, preliminary findings from the ongoing first-in-human, phase 1/2a KOMET-001 trial (NCT04067336) were presented, demonstrating activity with KO-539, an oral, selective menin inhibitor, in patients with relapsed/refractory AML. Moreover, the agent demonstrated activity in patients who harbored genomic mutations, including KMT2A and NPM1.

KMT2A mutations are associated with poor prognosis in patients with AML, says Jabbour. Currently, patients with KMT2A-mutant disease do not have any FDA-approved options available. Patients with NPM1 mutations tend to respond well to high-dose cytarabine, as well as venetoclax (Venclexta). However, patients with NPM1 mutations would benefit from additional treatment options, says Jabbour. Additionally, exploring KO-539 in combination with venetoclax may offer these patients a more effective treatment strategy compared with single-agent therapy, concludes Jabbour.