Inclusion Criteria:  Individuals eligible to participate in this study must meet all of the following:  All patients must meet the following criteria prior to the first dose of study drug:  Signed informed consent. Consent must be obtained prior to any study-related procedure. Age ≥60 years Histologically confirmed AML: Subjects must have de novo (primary) or secondary AML (any WHO 2016 classification excluding acute promyelocytic leukemia) who have either comorbidities and/or advanced age (≥ 75 years) that preclude use of intensive induction chemotherapy as determined by the investigator. Patients must be therapy-naïve (newly diagnosed) Patients must have CD123-positive AML as confirmed by centralized flow cytometry (or immunohistochemistry [IHC]). Patients with precedent MDS are eligible Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 Patients with previously untreated AML (by the World Health Organization (WHO) criteria, i.e. >/= 20% blasts). Prior biologic therapies (such as growth factors) and targeted therapies administered for the treatment of prior myelodysplastic syndrome are allowed (such as lenalidomide or luspatercept), with the exception of hypomethylating agents 5-azacytidine or decitabine. Patients must have been off such therapy for 1 week prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Hydroxyurea is permitted for control of counts prior to treatment. Life expectancy of > 2 months in the Investigator's opinion Creatinine ≤ 2.5 × upper limit of normal (ULN) Adequate liver test parameters: total bilirubin < 2.5 × ULN (if disease related or secondary to Gilbert's disease, then total bilirubin < 3.5 mg/dL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) < 5 × ULN Prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) < 2 × ULN  Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) may participate, provided they meet the following conditions:  Must agree to use physician-approved contraceptive methods (e.g., abstinence, intrauterine device, oral contraceptive, double barrier device) throughout the study and for 3 months following the last dose of APVO436; and Must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this study. Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 3 months following the last dose of APVO436  Exclusion Criteria:  Subjects with any of the following will not be eligible for study participation:  Acute promyelocytic leukemia (APL) with t(15;17) translocation Absolute peripheral blood myeloblast count greater than 20,000/mm3 - may receive hydroxyurea to reduce and control the myeloblast count down prior to and during the first week of the first cycle of treatment with study drug if necessary if deemed medically necessary and appropriate by the treating physician Patients with active central nervous system (CNS) involvement by AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor. History of seizures Prior solid organ transplant is acceptable provided the patient is on no immunosuppressive therapy. Any therapy or experimental treatment for AML within 7 days of the first dose of study drug. The use of hydroxyurea is acceptable and does not exclude the patient. Active, uncontrolled infection requiring systemic therapy. If the infection is controlled or has resolved, maintenance and/or prophylactic systemic antimicrobials are permitted. Major surgery within 3 weeks prior to first dose of study drug Known to be positive for HIV, hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) Uncontrolled hypertension, defined as blood pressure ≥ 140/90 mm Hg despite maximum medical intervention History of congenital long QT syndrome or torsades de pointes Pathologic bradycardia or heart block (excluding first degree heart block) Prolonged baseline QTc, defined as QTcF (Fredericia correction) interval >480 msec (other correction formulas may be used for patients with bundle branch block or ventricular pacemaker) History of ventricular arrhythmia (excluding PVCs) Major surgery within 28 days prior to informed consent Unstable angina pectoris within 28 days Myocardial infarction and/or new ST elevation or depression or new Q wave on ECG within 6 months Any history of stroke Symptomatic congestive heart failure Class III or greater (New York Heart Association Functional Classification) On full dose anti-coagulation defined as warfarin intended to raise the INR to 2-3 Major hemorrhagic event within 28 days requiring transfusion of packed red blood cells Prior history of hypertensive crisis or hypertensive encephalopathy Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture was performed to confirm the absence of leukemic blasts in the cerebrospinal fluid (CSF) Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) Any open wound Pregnant and nursing subjects are excluded because the effects of APVO436 on a fetus or nursing child are unknown Hydroxyurea is allowed prior to starting the study, and may be used for two weeks after dosing in Cycle 1 (e.g., Days 1-14 dosed with hydroxyurea) Substance use disorder, psychiatric, cognitive, or any other condition that, in the opinion of the Investigator, would pose a risk to the patient's safety, may compromise the patient's ability to understand and comply with the protocol or provide informed consent, or interfere with the study evaluation, study participation, or follow-up Any difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration, or may cause a safety concern for the patient Any uncontrolled medical condition, including but not limited to: Uncontrolled metabolic disorders such as hypercalcemia Any other active systemic malignancies. Exceptions: noninvasive non-melanoma skin cancer, in situ carcinoma, cervical intraepithelial neoplasia, and breast or prostate cancer that is well controlled with anti-hormonal therapy Any current autoimmune disorder requiring immunosuppressive therapy with more than a replacement dose of corticosteroids (i.e., > 10 mg/day of prednisone or equivalent)