Pivotal AUGMENT-101 trial of revumenib in r/r KMT2Ar acute leukemia meets primary endpoint and is stopped early for efficacy

The AUGMENT-101 trial met its primary endpoint at the protocol-defined interim analysis stage with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia cohort. The CR/CRh rate in patients with KMT2Ar AML was 24.5% (12/49). The CR/CRh responses in both the overall population and the AML subset were durable with a 6.4-month (95% CI: 3.4, NR) median duration as of the July 24, 2023 data cut-off, with 46% (6/13) remaining in response. Minimal residual disease (MRD) status was assessed in 10 of the 13 patients who achieved a CR/CRh, 70% (7/10) of whom were MRD negative.

In the efficacy-evaluable patients, the overall response rate was 63% (36/57; 95% CI: [49.3, 75.6]). A total of 14 (39%) patients who achieved an overall response underwent hematopoietic stem cell transplant (HSCT), eight of whom did not achieve a CR or CRh prior to transplant. Half (7/14) of the patients who had an HSCT received post-transplant maintenance with revumenib and three additional patients (3/14; 21%) were in follow-up and are eligible to restart revumenib as post-transplant maintenance.

Based on the Independent Data Monitoring Committee (IDMC) recommendation, the Company is stopping the trial to further accrual in the KMT2Ar cohorts. Syndax continues to expect to submit an NDA for revumenib for the treatment of R/R KMT2Ar acute leukemia to the FDA by year-end.

Revumenib was well tolerated and consistent with the Company's previously reported data. Treatment-related adverse events (TRAEs) leading to dose reductions and treatment discontinuation were low at 9% (8/94) and 6% (6/94), respectively. TRAEs of any grade in greater than 20% of patients included nausea (28%), differentiation syndrome (DS) (27%), and QTc prolongation (23%). Grade 3 DS was observed in 15% (14/94) of patients while one patient (1%) experienced Grade 4 DS and no patients experienced a Grade 5. Grade 3 QTc prolongation was observed in 14% (13/94) of patients, with no Grade 4 or 5 events. There were no discontinuations related to DS or QTc prolongation on the trial.

The Company has several trials of revumenib ongoing across the treatment landscape in mNPM1 and KMT2Ar acute leukemias. In addition to the clinical trials that Syndax is conducting, the Company is working with cooperative groups and leading investigators to further expand on the potential clinical benefit of revumenib. Syndax expects to achieve the following revumenib milestones by year-end: i. Present additional AUGMENT-101 data in R/R KMT2Ar acute leukemia patients at an upcoming medical meeting. ii. Present preliminary data illustrating revumenib's promising profile when combined with standard-of-care chemotherapy and venetoclax regimens. iii. Submit an NDA for the treatment of R/R KMT2Ar acute leukemias. iv. Complete enrollment of R/R mNPM1 acute leukemia patients in the AUGMENT-101 trial.