Syndax Pharmaceuticals presented positive data from the protocol-defined pooled analysis of the pivotal AUGMENT-101 trial of revumenib, a first-in-class menin inhibitor, in adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) at the 65thAmerican Society of Hematology (ASH) 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 (HSCT), were also featured in two poster presentations at the meeting, titled Revumenib Monotherapy in Patients With Relapsed/RefractoryKMT2Ar Acute Le leukemia: Efficacy and Safety Results From the AUGMENT-101 Phase 1/2 Study" and "Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant." Pivotal Phase 2 Portion of AUGMENT-101 Trial: The AUGMENT-101 trial met its primary endpoint at the protocol-defined interim analysis 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 population.

The CR/CRh rate was 23% (10/44; 95% CI: 11.5, 37.8) in adult patients and 23% in pediatric patients (3/13; 95% CI: 5.0, 53.8), with a median time to CR/CRh of 1.9 months (95% CI: 0.9, 4.5). 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 cutoff, 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 patients who achieved a CRc (CR+CRh+CRp+Cri), 68% (15/22) achieved MRD negative status. In the efficacy-evaluable patients, the overall response rate1 was 63% (36/57; 95% CI: [49.3, 75.6]), and the composite response rate (CRc) was 44% (25/57). Minimal residual disease (MRD) status was assessed in 22 of the 25 patients who achieved a CRc, 68% (15/22) 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 (39%) patients who achieved an overall response underwent 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.

Median overall survival at the time of data cutoff was 8.0 months (95% CI: 4.1, 10.9). 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 (56%; 32/57) relapsed following treatment with at least one salvage regimen (refractory relapse patients) prior to enrollment, including nearly half (46%; 26/57) having undergone prior stem cell transplant.

72% (41/57) of patients were previously treated with venetoclax. Revumenib Maintenance Therapy Post-HSCT: Data featured in a poster presentation from AUGMENT-101 Phase 1 patients who received revumenib maintenance therapy, including some ongoing for more than one year after HSCT, demonstrated revumenib duration of treatment in the maintenance setting at the time of this analysis ranged from 1 to 701 days, with treatment ongoing for nine of the 16 patients. CRc was maintained in 12 patients after HSCT and maintenance revumenib.

MRD negative remissions were maintained in six patients as of the data cutoff with one patient converting from an MRD+ to MRD- response. Three patients remain on revumenib maintenance therapy for more than one-year post-transplant. Phase 1 Portion of AUGMENT-101 Trial: In the Phase 1 portion of the study, patients were assigned to one of six dose-escalation cohorts designed to identify a recommended phase 2 dose (RP2D) for concomitant administration with a strong CYP3A4 inhibitor and without a strong CYP3A4 inhibitor.

As of the July 2023 data cutoff, 77 patients with R/R KMT2Ar acute leukemia were enrolled in the Phase 1 study and were included in the overall population. Most patients were female (60%), and 34% of patients had =4 prior lines of therapy and 47% had prior HSCT. Updated follow-up on Phase 1 data presented at the meeting continues to demonstrate clinically meaningful response, high percentage of responders proceeding to transplant, consistency of response across subgroups, and a manageable safety profile in heavily pretreated patients with R/R KMT2Ar acute leukemia.

Phase 1 KMT2Ar patients demonstrated a CR/CRh rate of 31.2%, and ORR of 64.9%, with 38% proceeding to HSCT. In adults with AML (n=51), the CR/CRh rate was 37.3% and ORR was 68.6%, with 40% of responders proceeding to HSCT. Pediatric patients (n=15) demonstrated consistent response rates, with a CR/CRh rate of 20.0% and an ORR of 66.7%, with 40% of responders proceeding to transplant.