Dr. Sallman on the Novel Menin Inhibitor KO-539 in AML

David Sallman, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the background of the menin inhibitor, KO-539, in acute myeloid leukemia (AML).

Menin plays a critical pathway for several subgroups of patients with AML, specifically in patients with MLL rearrangements and NPM1 mutations, Sallman says. KO-539 is one of several menin inhibitors under exploration for these subsets of patients with AML. KO-539 features a unique pharmacokinetic profile that permits for dosing once per day, and current pharmacokinetic data have not revealed any interactions with other medications used in this patient population, Sallman explains.

In December 2021, the phase 1b KOMET-001 trial (NCT04067336) was placed on a partial clinical hold by the FDA due to a patient death from a serious adverse effect (AE) that was potentially associated with differentiation syndrome. The partial clinical hold was lifted in January 2022. Differentiation syndrome a known AE related to differentiating agents in the treatment of patients with AML, and while differentiation syndrome is a class effect, the current data are too small to know if the risk of this AE is higher or lower with the use of KO-539 in this patient population when compared to other agents, Sallman concludes.