Syndax Pharmaceuticals presented positive data from multiple trials of Revuforj® (revumenib) in patients with acute leukemias at the 66th American Society of Hematology (ASH) Annual Meeting. The data highlight the potential of revumenib as a single-agent and in combination with standard of care agents.
SAVE Trial: Revumenib Combination Therapy in R/R AML
The Phase 1/2 SAVE trial evaluated an all-oral regimen of revumenib, venetoclax, and decitabine/cedazuridine in pediatric and adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or mixed-lineage acute leukemia (MPAL) harboring KMT2Ar, NUP98r, or mNPM1 alterations. Data from 33 patients were presented, with a median age of 35 years. The combination therapy achieved an overall response rate (ORR) of 82% (27/33) and a CR/CRh rate of 48% (16/33). Among patients with available minimal residual disease (MRD) data, 65% (17/26) who achieved a response were MRD negative, and 88% (14/16) of CR/CRh responders were MRD negative. Notably, 39% (13/33) of patients proceeded to hematopoietic stem cell transplantation (HSCT) following the combination, with 54% (7/13) resuming revumenib post-HSCT.
With a median follow-up of 9.3 months, the 6-month overall survival (OS) was 68% (95% CI: 47%, 80%). The median duration of CR/CRh response was not reached. The combination was generally well tolerated, with the most common Grade 3 or higher treatment-emergent adverse events (TEAEs) being febrile neutropenia (33%) and lung infection (33%).
AUGMENT-101 Trial: Revumenib in R/R KMT2Ar Acute Leukemia
Data from the Phase 2 portion of the AUGMENT-101 trial of revumenib in R/R KMT2A-rearranged (KMT2Ar) acute leukemia were presented. The efficacy population comprised 97 patients. The CR+CRh rate was 23% (22/97), the composite complete remission (CRc) rate was 42% (41/97), and the ORR was 64% (62/97). Among patients with MRD results available, 61% (11/18) of CR/CRh responders and 58% (21/36) of CRc responders achieved MRD negativity. Of the 62 patients who achieved ORR, 34% (21/62) proceeded to HSCT, and nine resumed revumenib post-HSCT.
Responses were observed across all major subgroups, including heavily pretreated patients and those with prior venetoclax exposure. The median time to ORR was 1.0 months, and the median time to CR/CRh was 2.0 months. The median duration of CR/CRh extended to 13 months among the 13 CR/CRh responders included in the interim analysis presented at the ASH Annual Meeting in 2023.
In the larger safety population (N=116), revumenib was generally well tolerated, with low rates of treatment-related adverse events (TRAEs) leading to treatment discontinuation (5%).
INTERCEPT Trial: Revumenib as Pre-Emptive Therapy for MRD Positive AML
The INTERCEPT trial is evaluating revumenib to target MRD and early relapse in AML. As of the latest data cutoff, 14 patients with MRD relapse (13 with mNPM1 and one with KMT2Ar) were enrolled in the safety cohort and received revumenib. Among the 11 efficacy evaluable mNPM1 patients, 54% (6/11) had MRD reduction at any time, including 36% (4/11) who achieved MRD negativity. These initial data support further evaluation of revumenib as a novel approach to targeting MRD relapse.
