Dr. Thirman on the Rationale for Using SNDX-5613 in Acute Leukemias

Michael J. Thirman, MD, associate professor of medicine, University of Chicago Medicine, discusses the rationale for using the investigational agent SNDX-5613 to treat a subtype of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Mixed lineage leukemia (MLL)-rearranged leukemias account for approximately 5-10% of all leukemias and 80% of infant acute leukemias. Currently, there are no approved treatments for patients with MLL-rearranged leukemias, which are associated with a poor prognosis.

Many centers around the world have been investigating MLL fusion proteins, says Thirman. Moreover, these laboratories have identified that the interaction between MLL and the menin protein is a key mediator in AML and ALL.

The highly specific, investigational, and potentially first-in-class compound SNDX-5613 blocks the MLL/menin interaction, explains Thirman. Preclinical cell lines and animal models demonstrated the compound’s efficacy in eliminating MLL-rearranged leukemia cells. Recent preclinical studies have also shown activity in NPM1-mutated AML.

SNDX-5613 is currently being evaluated in the phase I/II AUGMENT-101 trial for patients with relapsed/refractory leukemias, including those with an MLL/KMT2Aa gene rearrangement. One complete response has been noted in a patient with relapsed MLL-rearranged leukemia treated with SNDX-5613, concludes Thirman.