Syndax Reports Positive Results for Relapsed/Refractory mNPM1 AML in AUGMENT-101 Trial

Syndax Pharmaceuticals has unveiled promising results from the Phase 2 section of its AUGMENT-101 trial, which is investigating the efficacy of revumenib in patients with relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML). Revumenib is an oral small molecule menin inhibitor. The trial results have shown significant clinical benefits, meeting the primary endpoint of the study.

Among the efficacy-evaluable adults with R/R mNPM1 AML, a complete remission (CR) and CR with partial hematological recovery (CRh) rate of 23% was observed. Out of these, 12 patients achieved a CR while three obtained a CRh. The median duration of these responses was 4.7 months, and 64% of patients who achieved CR/CRh were found to be minimal residual disease (MRD) negative. The overall response rate (ORR) in this heavily pretreated population was 47%, with 75% of these patients having prior exposure to venetoclax. Notably, 17% of those who achieved a response underwent hematopoietic stem cell transplant (HSCT) following revumenib treatment, with some resuming the therapy post-transplant.

Michael A. Metzger, CEO of Syndax, expressed optimism about the results, indicating that they could significantly impact the estimated 40% of AML patients with specific genetic alterations. The study, which included 64 adult patients with a median age of 65, highlighted the compelling and consistent clinical profile of revumenib across various treatment settings.

The safety analysis, which included 84 adult and pediatric patients, revealed that the safety profile of revumenib was consistent with previously reported data. The incidence of treatment-related adverse events (TRAEs) leading to treatment discontinuation was low, at 5%. TRAEs of Grade 3 or higher occurring in more than 10% of patients included QTc prolongation, anemia, febrile neutropenia, differentiation syndrome, and decreased platelet count. Importantly, there were no Grade 5 TRAEs reported.

Dr. Eytan M. Stein from Memorial Sloan Kettering Cancer Center emphasized the significance of these results, particularly given the challenging nature of relapsed or refractory mNPM1 AML. The robust response rates and the encouraging safety profile point to the potential of revumenib as a promising treatment option for this patient population.

Looking ahead, Syndax is planning several key milestones for revumenib. These include seeking FDA approval for the treatment of R/R KMT2A-rearranged (KMT2Ar) acute leukemias by the end of 2024 and presenting further data at the American Society of Hematology (ASH) Annual Meeting in December 2024. The company also aims to initiate a pivotal combination trial with venetoclax/azacitidine in newly diagnosed mNPM1 AML or KMT2Ar acute leukemias by the end of 2024. Additionally, Syndax plans to submit a supplemental New Drug Application (sNDA) for the treatment of R/R mNPM1 AML in the first half of 2025.

Revumenib is a groundbreaking therapy that targets the menin-KMT2A binding interaction, crucial in treating KMT2A-rearranged and mNPM1 acute leukemias. Previously, the U.S. FDA has granted it Orphan Drug Designation for AML, ALL, and acute leukemias of ambiguous lineage, along with Fast Track and Breakthrough Therapy designations for treating adult and pediatric patients with R/R acute leukemias harboring KMT2A rearrangement or NPM1 mutation.

The Phase 1/2 AUGMENT-101 trial is an open-label, multi-center study evaluating the safety, tolerability, pharmacokinetics, and efficacy of revumenib. The trial's expansion part focuses on patients with R/R KMT2Ar AML, KMT2Ar ALL, and mNPM1 AML, assessing efficacy through CR and CRh rates, as well as safety and tolerability.

Mutations in the NPM1 gene are the most common genetic alterations in adult AML, present in about 30% of cases. Patients with relapsed or refractory mNPM1 AML have a poor prognosis with limited treatment options. Revumenib's development offers hope, addressing a significant unmet need in this patient group.

Syndax Pharmaceuticals, with its innovative pipeline, is committed to advancing cancer care. The company continues to conduct clinical trials and explore the full potential of its therapies, aiming to bring effective treatments to patients with high unmet medical needs.