FHD-286

FHD-286: 2.5 or 5 mg (based on assigned dose group) PO (capsules) once daily (QD) 5 days/week (days 3-7, 10-14, 17-21, and 24-28 of each 28-day cycle) If acceptable safety and tolerability are observed at the end of cycle 1 with at least 3 DLT-evaluable participants in cohort 1 (FHD-286 2.5 mg QD), the dose of FHD-286 will be escalated to 5 mg QD for cohort 2. Doses of DAC and VEN will not change The 2 non-dosing days must be the day of and the day after the VEN dose * If necessary to improve tolerability and/or…

Decitabine: 0.2 mg/kg/day subcutaneously once weekly (QW) (days 1, 8, 15, 22 [±3 days] of each 28-day cycle) - A second weekly dose may be added if the investigator determines that more rapid debulking is required for a participant with high disease burden. The 2 weekly DAC doses should, preferably, be given on consecutive days

This study evaluates the addition of FHD-286, which has a distinct mechanism of action and clinical activity in AML, to a modification of the current standard of care regimen (DAC/VEN) that has been shown to be more tolerable than and have similar clinical activity as the more intensive regimen evaluated in the VIALE-A study (see References section). Total duration of trial intervention for each participant will vary.

This is a Phase 1, uncontrolled, single-arm, open-label, nonrandomized, dose escalation, study of Decitabine (DAC)+Venetoclax (VEN)+FHD-286 in participants with newly diagnosed Acute Myeloid Leukemia (AML) classified as adverse risk per the 2022 European Leukemia Net (ELN) criteria or AML that has progressed after one prior line of therapy.

Live record on ClinicalTrials.gov →

• Newly diagnosed adverse risk AML, including Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), per the 2022 ELN criteria, with a histopathologic diagnosis confirmed by hematopathology review OR AML that has progressed after 1 prior line of therapy with ≥5% blasts
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or 3
• Cardiac history of congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina pectoris
• Diffusing capacity of the lung for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.