APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies

Inclusion Criteria: 1. Signed informed consent and ability to comply with protocol requirements. 2. Documented diagnosis of AML according to World Health Organization WHO) classification 3. Adequate organ function as defined by the following laboratory values: 1. Creatinine clearance \> 30 mL/min 2. Total serum bilirubin \< 1.5 × ULN 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 × ULN 4. Age ≥18 years 5. At least one TP53 mutation 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 7. Projected life expectancy of ≥ 12 weeks. 8. Negative serum or urine pregnancy test 9. Females of childbearing potential and males with female partners of childbearing potential must be willing to use an effective form of contraception Exclusion Criteria: 1. Prior treatment for TP53-mutant AML (\*dependent upon treatment arm assigned). 2. Known history of HIV or active hepatitis B or active hepatitis C infection. 3. Any of the following cardiac abnormalities: 1. Myocardial infarction within six months prior to registration; 2. New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction (LVEF) \< 40%; 3. A history of familial long QT syndrome; 4. Symptomatic atrial or ventricular arrhythmias 5. QTcF ≥ 470 msec, unless due to underlying bundle branch block and/or pacemaker and with approval of the medical monitor. 4. Concomitant malignancies for which patients are receiving active therapy 5. Known active CNS involvement from AML. 6. Malabsorption syndrome 7. Pregnancy or lactation. 8. Active uncontrolled systemic infection (viral, bacterial or fungal).