Syndax Pharmaceuticals has presented positive data from multiple trials of Revuforj (revumenib) as a single-agent and in combination with standard of care agents in patients with acute leukemias in oral sessions at the 66th American Society of Hematology (ASH) Annual Meeting being held in San Diego.

Revuforj is the company's oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

"On the heels of the recent approval of Revuforj for R/R acute leukemia with a KMT2A translocation, we are excited to present clinical data highlighting the consistent efficacy and favorable tolerability of this first-in-class therapy, as both a single-agent and in combination with standard of care, in patients with mNPM1 and KMT2Ar acute leukemia," said Michael A. Metzger, Chief Executive Officer.

"We are thrilled that our U.S. launch of Revuforj is firmly underway, and we look forward to building on this momentum as we continue to advance our clinical development program which we believe will position us to pursue meaningful label expansion opportunities," added Metzger.

The Phase 1/2 SAVE trial is an investigator-sponsored trial testing an all-oral regimen of revumenib, venetoclax and the hypomethylating agent (HMA) ASTX727 (decitabine/cedazuridine) in pediatric and adult patients with R/R acute myeloid leukemia (AML) or mixed-lineage acute leukemia (MPAL) harboring either KMT2Ar, NUP98r or mNPM1 alterations.

During the oral session at the ASH meeting, data from 33 patients were presented (DCO: November 2024). The median age of patients enrolled in the trial was 35 (range 12-81), and 16 patients (49 percent) had KMT2Ar, 12 patients (36 percent) had mNPM1, and five patients (15 percent) had NUP98r. Patients had received a median of three (range: 1-5) prior lines of therapy; 58% had prior venetoclax, 36 percent had prior hematopoietic stem cell transplantation (HSCT), and 6% had received a prior menin inhibitor. 

The all-oral combination resulted in high rates of remission in patients with KMT2Ar, mNPM1, and NUP98r with an overall response rate (ORR)1 of 82 percent (27/33) and a CR/CRh rate of 48 percent (16/33). In patients with minimal residual disease (MRD) status available, 65 percent (17/26) who achieved a response were MRD negative, and among patients who achieved a CR/CRh response, 88 percent (14/16) were MRD negative. 39 percent (13/33) of patients proceeded to HSCT following this combination, with 54 percent (7/13) of patients resuming revumenib post-HSCT.

"The latest SAVE data show high efficacy and the ability to combine revumenib with venetoclax and hypomethylating agents, which highlights the potential for this combination to become a treatment for patients with acute leukemias that are susceptible to menin inhibition," said Ghayas C. Issa, MD, Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center.

"In particular, the high rates of overall response, MRD negativity, and HSCT in the R/R cohort are very encouraging, as well as the initial duration of response and overall survival data. These promising data underpin our excitement to expand the SAVE trial to evaluate the combination in newly diagnosed AML patients who are older or unfit for intensive chemotherapy," Issa added.