If you choose to join this study, you will go through a screening period to find out if you are eligible. During this screening period, you will:

• Have a physical exam
• Have a heart scan (ECG)
• Have blood draws
• Have cancer cells tested for the presence of the NPM1 mutation and KMT2A rearrangement along with FLTe or other mutations

After the screening period, you will begin the study drug period. This part of the study is divided into 2 parts. Part 1a (dose escalation) is to determine the safest, most effective dose of the study drug in combination with other cancer drugs. Part 1b (dose validation expansion) will happen once the most appropriate combinations and dose levels have been determined from Part 1a. Part 1a will be made up of the following cohorts:

• A-2: The study drug will be given in combination with cytarabine plus daunorubicin in patients who have never been treated for AML and have an NPM1 mutation
• B-2: The study drug will be given in combination with cytarabine plus daunorubicin in patients who have never been treated for AML and have a KMT2A rearrangement
• A-1: The study drug will be given in combination with venetoclax and azacitidine in patients who have been treated for AML but did not respond to therapy and have an NPM1 mutation
• B-1: The study drug will be given in combination with venetoclax and azacitidine in patients who have been treated for AML but did not respond to therapy and have a KMT2A rearrangement

Part 1b will be made up of the following cohorts:

• A-3: The study drug will be given in combination with venetoclax in patients who have been treated but have not responded to standard therapy and have an NPM1 mutation
• A-4: The study drug will be given in combination with venetoclax and azacitidine in patients who have never been treated for AML and have an NPM1 mutation
• B-3: The study drug will be given in combination with venetoclax and azacitidine in patients who have never been treated for AML and have a KMT2A rearrangement

Whether you are in Part 1a or Part 1b of the study will depend on when you join the study. The cohort to which you are assigned in either part will depend on your diagnosis and treatment history. Each study drug cycle is 28 days. You will start taking the study drug on Day 8 of each cycle, unless you are enrolled in cohort A-3. If you are enrolled in Cohort A-3, you will start taking the study drug on Day 1. The study drug is taken by mouth. All other drugs are given by IV infusion or by subcutaneous injection. The number of study drug cycles you do will depend on how you tolerate the regimen, how your cancer responds to the regimen, and your overall wellbeing.