Treatment schema with dose levels and schedules tested. Diagram of the study design and participants. (Top) TAG and AZA were first tested as a doublet combination at 5 different doses/schedules of TAG with 7-day dosing of AZA. The RP2D of TAG was determined to be 12 μg/kg daily for 3 days (d1, 2, 3; in magenta) in combination with AZA. Patients with AML or MDS were eligible in Cohorts A1-A4. While cohort A4 was being enrolled, AZA-VEN was approved for AML. Therefore, the study was amended and cohort A5 was limited to MDS. (Bottom) 3 doses of TAG were tested with AZA-VEN as a triplet in patients with AML. In the first cycle, VEN was given as 100 mg on day 1, 200 mg on day 2, and 400 mg on day 3, followed by 400 mg on days 4 to 21. In subsequent cycles, VEN was given as 400 mg on days 1 to 21. The RP2D of TAG was determined to be 12 μg/kg daily for 3 days (d4, 5, 6; in magenta) in combination with AZA-VEN. Patients with 1L or R/R AML were eligible in dose escalation, and then separate expansion cohorts in 1L and R/R AML were enrolled.