A Study to Investigate APL-4098 Alone and in Combination in Adults With AML or MDS

Who May Qualify: - 18 years or older - Confirmed diagnosis of relapsed refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS)/ AML, or MDS-excess blasts (MDS-EB) with the following characteristics: - R/R AML (primary or secondary, including treatment-related), participant is intolerant to, or considered ineligible for available therapies known to provide clinical benefit. - WBC count ≤ 25,000/microliter - ECOG Performance Status of ≤ 2 - Weight ≥ 40kg - Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse - Male participants must be willing to use specific contraception and not plan to impregnant a female partner or donate sperm while on study - Participant must be willing and able to provide written willing to sign a consent form and to comply with the requirements of the trial Who Should NOT Join This Trial: - Certain prior therapies such as: received an allogeneic stem cell transplant within 6 months of screening, received an autologous stem cell transplant within 3 months of screening, received any anti-cancer treatments within 2 weeks of Cycle 1 Day 1, prior radiation therapy within 4 weeks of screening - Certain medical conditions such as: other malignancies, myocardial infarction within 6 months of screening, symptomatic congestive heart failure, uncontrolled active infection, history of arterial thrombosis within 6 months of screening - Diagnostic assessments: Left ventricular ejection fraction \< 45%, Fridericia's corrected QT interval \> 470msec, Aspartate aminotransferase and/or alanine aminotransferase \> 3 x upper limit of normal (ULN), total bilirubin \> 1.5 x ULN, calculated or measured creatinine clearance \< 45 mL/minute (multiply by 0.85 if female) - Infectious disease: HIV positive, active hepatitis B and/or C Always talk to your doctor about whether this trial is right for you.