Syndax Publishes AUGMENT-101 Revumenib Trial Data in Journal of Clinical Oncology

WALTHAM, Mass., Aug. 12, 2024 -- Syndax Pharmaceuticals, a clinical-stage biopharmaceutical company, announced that data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib have been published in the Journal of Clinical Oncology. Revumenib is a first-in-class menin inhibitor used in adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL).

Neil Gallagher, M.D., Ph.D., President and Head of Research and Development at Syndax, emphasized the significance of the data publication, noting that it allows broader dissemination of critical findings and underpins the NDA filing currently under FDA review. Gallagher added that the company is preparing for a commercial launch to make the medicine available to those in need.

Dr. Ghayas C. Issa from The University of Texas MD Anderson Cancer Center highlighted the lack of adequate available therapies for KMT2Ar acute leukemia patients, despite an improved understanding of the disease mechanisms. He expressed optimism that revumenib could become a paradigm-changing treatment due to its high rate of deep, MRD-negative responses and a safety profile that supports prolonged therapy and maintained remission post-stem cell transplant.

The FDA has granted Priority Review for the New Drug Application (NDA) for revumenib for treating adult and pediatric R/R KMT2Ar acute leukemia. The NDA is being reviewed under the FDA's Real-Time Oncology Review Program (RTOR) with a target action date of December 26, 2024.

In March 2024, Syndax completed enrollment in the final AUGMENT-101 pivotal trial cohort of patients with R/R mutant nucleophosmin (mNPM1) AML. Topline data is expected in the fourth quarter of 2024, which could support a supplemental NDA filing for revumenib in R/R mNPM1 AML in the first half of 2025.

The Journal of Clinical Oncology publication titled "Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)" presents positive data from 94 acute leukemia patients as of July 2023. Fifty-seven of these patients, who had central confirmation of their KMT2Ar status, were part of the efficacy analysis. The trial met its primary endpoint with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% among the 57 efficacy-evaluable patients.

Among adult patients, the CR + CRh rate was 23%, and similarly, it was 23% in pediatric patients. The median time to CR + CRh was 1.9 months, and the responses were durable, with a median duration of 6.4 months. Minimal residual disease (MRD) status was achieved in 70% of patients who reached CR + CRh.

The overall response rate (ORR) was 63%, and the composite response rate (CRc) was 44%. Responses were observed across various subgroups and age ranges. Additionally, 14 patients who achieved an overall response underwent hematopoietic stem cell transplant (HSCT), and half of these resumed revumenib treatment post-transplant. Median overall survival at the data cutoff was 8.0 months.

Revumenib's safety profile was consistent with previous reports. In the AUGMENT-101 trial safety population, treatment-emergent adverse events (TEAEs) of Grade ≥3 included febrile neutropenia, neutropenia, thrombocytopenia, anemia, differentiation syndrome, QTc prolongation, sepsis, and hypokalemia. TEAEs leading to dose reduction or discontinuation were low.

Revumenib is being developed for KMT2A-rearranged (KMT2Ar) acute leukemias, including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial were presented at the American Society of Hematology Annual Meeting, and full data have now been published. Revumenib has received multiple designations from the FDA and the European Commission for its potential to treat AML and ALL.

Syndax Pharmaceuticals is focused on developing cancer therapies, including revumenib, a highly selective menin inhibitor, and axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor.