A Phase 1 Study of AOH1996 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• Age: ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Life expectancy > 3 months

• Patients with histologically confirmed AML, according to International ConsensusClassification (ICC) or World Health Organization (WHO) criteria, withrefractory/relapsed (R/R) disease who have failed treatment with, or are ineligiblefor, available therapies known to be effective for treatment of their AML

• Patients with extramedullary disease may be included if they also have marrowinvolvement

• Patients with acute promyelocytic leukemia (APL) will not be eligible

• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prioranti-cancer therapy

• Ability to swallow pills

• White blood cell (WBC) ≤ 25 x 10^9/L prior to initiation of study therapy.Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may berequired (within 14 days prior to day 1 of protocol therapy)

• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (within 14 days prior to day 1of protocol therapy)

• Aspartate aminotransferase (AST) =< 3.0 x ULN (within 14 days prior to day 1 ofprotocol therapy)

• Alanine aminotransferase (ALT) =< 3.0 x ULN (within 14 days prior to day 1 ofprotocol therapy)

• Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gaultformula (within 14 days prior to day 1 of protocol therapy)

• International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN (within 14 daysprior to day 1 of protocol therapy)

• Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 14 days prior today 1 of protocol therapy)

• Corrected QT interval (QTc)F ≤ 480 ms based on Fridericia's formula

• Note: To be performed within 28 days prior to day 1 of protocol therapy

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)

• If the urine test is positive or cannot be confirmed as negative, a serumpregnancy test will be required

• Agreement by females and males of childbearing potential* to use an effective methodof birth control (nonhormonal) or abstain from heterosexual activity for the courseof the study through at least 2 months after the last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Hematopoietic stem cell transplant within 100 days prior to day 1 of protocoltherapy. Patients who have stopped calcineurin inhibitors (CNI) must be off CNIs forat least 2 weeks prior to day 1 of protocol therapy

• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 daysprior to day 1 of protocol therapy with the following exception of hydroxyurea whichis allowed prior to treatment and through cycle 1 for control of rapidly progressingleukemia

• Strong inducers or strong inhibitors of CYP enzymes (e.g., 1A2, 2B6, 2C8, 2C9, 2C19,and 3A4), other than azole antifungals with CYP3A4 inhibition potential, or drugtransporters (e.g., organic anions [OATP1B1/1B3], BCRP, P-gp, organic cations [OCT1,OCT2, OCT3], MATE1 or MATE2K), or sensitive substrates of these CYPs or drugtransporters, within 4-5 half-lives or 14 days prior to the first dose of studydrug, whichever is longer.

• Foods/supplements that are strong inhibitors or strong or moderate inducers of CYP3A (such as St. John's wort) within 3 days prior to initiation of and during studytreatment

• Systemic steroid therapy > 10 mg/day (≤ 10mg/day prednisone equivalent ok) or anyother form of immunosuppressive medication within 14 days. Inhaled or topicalsteroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent,are permitted

• Must not have received or planning to receive live vaccine while being on study or 4weeks before and after completion of treatment

• Patients with blast phase chronic myeloid leukemia (CML)

• Patients with translocation (t)(15;17) karyotypic abnormality or acute promyelocyticleukemia (French-American-British [FAB] class M3-AML)

• Active central nervous system (CNS) disease

• Active graft versus (vs) host disease (GVHD)

• Unstable cardiac disease as defined by one of the following:

• Cardiac events such as myocardial infarction (MI) within the past 6 months

• Uncontrolled atrial fibrillation or hypertension

• No measurable disease in the bone marrow

• Gastrointestinal disorder that interferes with oral drug absorption such asmalabsorption syndrome

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to study agent

• Uncontrolled active infection

• Clinically significant uncontrolled illness

• Other active malignancy. Patients with a prior or concurrent malignancy whosenatural history or treatment does not have the potential to interfere with thesafety or efficacy assessment of the investigational regimen are eligible for thistrial

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)