Acute Myeloid Leukemia (AML) Clinical Trials

• 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

• Aged ≥75 years, or aged 18-74 years and either refuse to receive intensive induction chemotherapy or are not a candidate for intensive induction chemotherapy due to one or more of the following comorbidities:

∙ 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%

‣ Creatinine clearance ≥30 mL/min to \<45 mL/min

‣ Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0×upper limit of normal (ULN)

‣ Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy

• Bone marrow blasts ≥10%

• Have not received a hypomethylating agent (HMA) or VEN for their disease under study

• No other disease-directed therapy, except hydroxyurea or cytarabine, and including experimental or investigational drug therapy, for at least 14 days before study entry

• ECOG PS:

∙ New diagnosed AML:

⁃ 75 years: ≤2

• 18 years to \<75 years: ≤3

‣ AML that has progressed after 1 prior line of therapy (Any age):

⁃ 3 if R/R AML

• Life expectancy ≥3 months

• Adequate end organ function, defined as:

∙ Adequate hepatic function, including:

⁃ Serum total bilirubin ≤3.0×ULN, unless considered due to advanced hematologic malignancy involvement or documented Gilbert syndrome with direct bilirubin ≤1.5×ULN

• Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≤3.0×ULN, unless considered due to advanced hematologic malignancy involvement

‣ Prothrombin time ≤1.5×ULN or international normalized ratio ≤1.4

‣ Activated partial thromboplastin time ≤1.5×ULN Note: Individuals who have been receiving a stable dose of anticoagulation therapy without bleeding episodes for ≥12 weeks may be considered for the study

‣ No known portal vein thrombosis

‣ Glomerular filtration rate (GFR) ≥30 mL/min (based on a contemporary, widely accepted, and clinically applicable equation that estimates GFR or a measure of GFR)

• Adequate cardiovascular, respiratory, and immune system function as evidenced by the below criterion and in the opinion of the investigator:

• a. Left ventricular ejection fraction (LVEF) of ≥40% by echocardiogram (ECHO)

⁃ White blood cell count ≤20×10\^9/L (treatment with hydroxyurea or cytarabine ≤1 g/m2 to achieve this count is allowed before the start of study treatment and for up to 28 days after the start of study treatment)

⁃ Agree to abide by dietary and other considerations required during the study

⁃ Ability to understand and willingness to sign a written informed consent form and complete study-related procedures