SNDX-5613, a potent, highly selective, oral inhibitor of the menin-mixed lineage leukemia (MLL) binding interaction, is currently under investigation in the phase I/II AUGMENT-101 trial (NCT04065399) for the treatment of patients with relapsed/refractory acute leukemias. Very recently, it was announced that SNDX-5613 yielded an overall response rate of 48% in patients harboring MLL rearrangement and NPM1c mutation.1
Preclinical and preliminary clinical data from the AUGMENT-101 trial demonstrated single-agent activity and rapid response after a single 28-day cycle. For more information on the study design and initial results, click here.
By a cutoff date of March 12, 2021, a total of 43 heavily pretreated patients, with a median of three prior therapies, received SNDX-5613 in the phase I trial. Among evaluable patients for efficacy (n = 31), the overall response rate in patients with MLL-rearranged (MLL-r) and those with NPM1c mutation was 54% and 29%, respectively. Among responders, 67% achieved minimal residual disease negativity. There were no treatment discontinuations due to treatment-related adverse events, suggesting good tolerability.
The trial will continue into phase II and the efficacy of SNDX-5613 will be evaluated in three different expansion cohorts, including MLL-r acute lymphoblastic leukemia, MLL-r acute myeloid leukemia (AML), and NPM1c+ AML.
SNDX-5613 holds orphan drug designation by the U.S. Food and Drug Administration (FDA) for adult and pediatric AML.2