Syndax reports new data from BEAT AML trial of revumenib/venetoclax/azacitidine

Syndax Pharmaceuticals announced updated data from multiple combination trials of revumenib, the company’s potent, selective, small molecule menin inhibitor, in patients with acute leukemias. The updated data are being presented at the European Hematology Association 2024 Congress, being held June 13-16 in Madrid, Spain and virtually. The company announced updated data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mutant nucleophosmin or KMT2A-rearranged acute myeloid leukemia patients aged 60 years or older in an oral presentation titled “Phase 1b Study of Azacitidine, Venetoclax and Revumenib in Newly Diagnosed Older Adults with NPM1 Mutated or KMT2A Rearranged AML: Interim Results of Dose Escalation from the BeatAML Consortium.” The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with a strong CYP3A4 inhibitor beginning on day 1 of a 28-day cycle in combination with on label doses of venetoclax and azacitidine. As of the data cutoff date of May 1, 2024, 26 newly diagnosed mNPM1 or KMT2Ar AML patients were enrolled. In the efficacy evaluable population, the composite complete remission rate was 96% and 92% of patients also attained minimal residual disease negative status as determined by central flow cytometry. Three patients proceeded to hematopoietic stem cell transplant (HSCT). The first cohort of patients treated in the trial, at 113 mg, had extended follow-up and an estimated 12-month survival of 100%. Revumenib was dosed safely at both the 113 mg and 163 mg q12h dose in combination with venetoclax and azacitidine. 15% of patients experienced differentiation syndrome with one Grade 3 event. 46% of patients experienced QTc prolongation with three Grade 3 events. All DS and QTc prolongations were self-limiting and resolved without complication or the need for revumenib dose reductions. Venetoclax was dosed in accordance with its label and an analysis of the onset and extent of hematologic toxicities suggest a similar experience to what has been reported for the venetoclax/azacytidine doublet. Overall, there were no new or increased safety signals observed when revumenib was added to this triplet combination. An expansion cohort is ongoing at both dose levels to establish the recommended dose for future trials. The company plans to initiate a pivotal trial with this combination in front-line newly diagnosed patients by year-end 2024.