A PHASE 1 STUDY OF REVUMENIB, AZACITIDINE, AND VENETOCLAX AND IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA

Dr. Hiroto Inaba, M.D. – St. Jude Children's Research Hospital, Inc., Memphis, TN

Although survival rates for children with AML are greater than 60%, the outcome for patients with relapsed or refractory disease remains poor, with less than 40% of these patients becoming long term survivors. Therefore, novel approaches are urgently needed, both for the treatment of patients who have relapsed and for incorporation into treatment regimens for newly diagnosed patients. Because AML is a genetically and biologically diverse group of diseases, a rational approach is to develop and test novel therapies in patients who are predicted to respond to those agents. Exciting and extensive preclinical data strongly suggest that menin inhibitors will be active in patients with specific genetic alterations. Preclinical data also demonstrate that the combination of a menin inhibitor with a BCL2 inhibitor is synergistic, as is the combination of a BCL2 inhibitor with a hypomethylating agent. Our proposed RAVAML trial will be the first pediatric trial to test the combination of all three classes of agents, including revumenib (a menin inhibitor), azacitidine (a hypomethylating agent), and venetoclax (a BCL2 inhibitor). We strongly believe that this trial will facilitate the development of menin inhibitor therapy for children with AML and will help move this novel and effective therapy into the frontline setting, ultimately changing the treatment paradigm for children with AML.