Syndax Pharmaceuticals, Inc. announced completion of enrollment in the AUGMENT-101 pivotal trial cohort of patients with relapsed/refractory (R/R) mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML). Topline data is expected in the fourth quarter of 2024 and could support a supplemental New Drug Application (sNDA) filing for revumenib in R/R mNPM1 AML in the first half of 2025. 64 adult and up to 20 pediatric patients with mNPM1 AML have been enrolled into the pivotal portion of AUGMENT-101, a pivotal trial designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of orally administered revumenib.

The primary endpoint for the trial is efficacy as measured by complete remission (CR) or a CR with partial hematological recovery (CRh) rate (CR + CRh) per protocol, with secondary endpoints including duration of response (DOR) and overall survival (OS). A new drug application (NDA) is under review by the U.S. Food and Drug Administration (FDA) for revumenib in R/R KMT2Ar acute leukemia with a Prescription Drug User Fee Act (PDUFA) action date of September 26, 2024. The NDA submission is supported by positive data from the AUGMENT-101 pivotal trial cohort of revumenib in adult and pediatric patients with KMT2Ar AML and acute lymphoblastic leukemia (ALL).

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology Annual Meeting and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. NPM1-mutant AML, which is distinguished by mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases.

This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to KMT2A-rearranged acute leukemia, NPM1-mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. NPM1-mutant AML is routinely diagnosed through currently available screening techniques.

There are currently no approved therapies indicated for NPM1-mutant AML.