Syndax says AUGMENT-101 trial of revumenib met primary endpoint

Syndax Pharmaceuticals presented data from the protocol-defined pooled analysis of the pivotal AUGMENT-101 trial of revumenib, a menin inhibitor, in adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia at the 65th American Society of Hematology Annual Meeting being held December 9-12, 2023 in San Diego, California. The pivotal results were featured in a late-breaking oral presentation titled “Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal AUGMENT-101 Phase 2 Study.” Additional supportive results from the AUGMENT-101 trial, including data from patients in the Phase 1 portion and patients who received revumenib maintenance therapy after hematopoietic stem cell transplant, were also featured in two poster presentations at the meeting, titled “Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Efficacy and Safety Results from the AUGMENT-101 Phase 1/2 Study” and “Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant.” The AUGMENT-101 trial met its primary endpoint at the protocol-defined interim analysis with a complete remission or a CR with partial hematological recovery rate of 23% among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia population. The CR/CRh rate was 23% in adult patients and 23% in pediatric patients, with a median time to CR/CRh of 1.9 months. The CR/CRh responses in both the overall population and the AML subset were durable with a 6.4-month median duration as of the July 24, 2023 data cutoff, with 46% remaining in response. Minimal residual disease status was assessed in 10 of the 13 patients who achieved a CR/CRh, 70% of whom were MRD negative. In patients who achieved a CRc, 68% achieved MRD negative status. In the efficacy-evaluable patients, the overall response rate was 63%, and the composite response rate was 44%. Minimal residual disease status was assessed in 22 of the 25 patients who achieved a CRc, 68% of whom were MRD negative. Responses were observed in all major subgroups, including across the number of prior treatments and prior stem cell transplant. A total of 14 patients who achieved an overall response underwent HSCT, eight of whom did not achieve a CR or CRh prior to transplant. Half of the patients who had an HSCT received post-transplant maintenance with revumenib and three additional patients were in follow-up and are eligible to restart revumenib as post-transplant maintenance. Median overall survival at the time of data cutoff was 8.0 months. AUGMENT-101 enrolled a total of 94 acute leukemia patients in the KMT2Ar cohorts of the pivotal trial as of the July 2023 data cutoff, 57 of whom had central confirmation of their KMT2Ar status, sufficient follow-up and were in the efficacy-evaluable population. The majority of patients included in the efficacy-evaluable population relapsed following treatment with at least one salvage regimen prior to enrollment, including nearly half having undergone prior stem cell transplant. Seventy-two percent of patients were previously treated with venetoclax. Revumenib was well tolerated and the safety profile was consistent with the Company’s previously reported data. Treatment-related adverse events leading to dose reductions and treatment discontinuation were low at 9% and 6%, respectively. TRAEs of any grade in greater than 20% of patients included nausea, differentiation syndrome, and QTc prolongation. Grade 3 DS was observed in 15% of patients while one patient experienced Grade 4 DS and no patients experienced a Grade 5. Grade 3 QTc prolongation was observed in 14% of patients, with no Grade 4 or 5 events. There were no discontinuations related to DS, cytopenias or QTc prolongation on the trial.