Multicenter phase 2a study of iadademstat plus azacitidine for newly diagnosed acute myeloid leukemia

Iadademstat is an oral inhibitor of the transcriptional repressor LSD1 (aka KDM1A), that showed promising early activity in a phase 1 trial of acute myeloid leukemia (AML). In AML cell lines, synergy of iadademstat and azacitidine was seen. The phase 2a dose-finding ALICE study, at 6 centers in Spain, evaluated the combination of iadademstat and azacitidine for newly diagnose AML. The recommended phase 2 dose was oral iadademstat 90 μg/m² five days on two days off weekly plus subcutaneous azacitidine 75 mg/m² for 7 of 28 days. Objective response was seen in 22 of 27 evaluable patients (82%; 95% CI 62-94), with complete remission in 14 of 27 patients (52%), and MRD-negative remission in 10 of 11 evaluable patients. The authors conclude that the combination of iadademstat and azacitidine had a manageable safety profile and showed promising responses in patients with newly diagnosed AML.