Phase 1 Open-label Study of AMX-883 Alone in Participants With AML and High-risk MDS and in Combination in Participants With AML

Inclusion Criteria: * Participants with relapsed or refractory AML who have failed all available standard therapies or relapsed or refractory high-risk MDS with BM blasts 10-19% * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Adequate washout from prior therapies * Adequate kidney and liver function * Female participants of childbearing potential must use highly effective contraception for at least 120 days, or 27 weeks (applicable to the United Kingdom \[UK\] only), after last dose, and male participants must agree to use barrier contraception and avoid sperm donation for at least 120 days after last dose * If enrolled in M1B: Participant must have no documented contraindication to treatment with posaconazole before start of treatment Exclusion Criteria: * Diagnosis of acute promyelocytic leukaemia or chronic myelogenous leukaemia in blast crisis * Clinically active central nervous system (CNS) leukaemia * Receiving immunosuppressive therapy post HSCT * History of another malignancy that is active, progressing, or has required systemic treatment within the past 2 years * Presence of \>Grade 1 active graft versus host disease within 4 weeks prior to C1D1 * Significant cardiovascular disease * Family history of sudden cardiac death before 40 years of age or a family history of long QT syndrome * Clinically significant electrolyte imbalances (e.g., hypokalaemia, hypomagnesaemia, hypocalcaemia) that may contribute to QT interval prolongation * Clinically significant bradycardia (\<50 beats per minute) that is symptomatic or causes haemodynamic instability * Major surgery within 4 weeks prior to C1D1 or inadequate recovery from prior surgery * Uncontrolled intercurrent illness * Inability to fast, swallow, ingest, or absorb oral medication due to a pre-existing condition * History of interstitial lung disease or pneumonitis requiring systemic corticosteroid treatment * Requirement for medications with a known risk of Torsades de Pointes that cannot be discontinued prior to study treatment * Detectable human immunodeficiency virus (HIV) viral load (applicable to rest of the world) * Known history of human immunodeficiency virus (HIV)-1/2 antibodies with an HIV ribonucleic acid (RNA) viral load ≥50 copies/mL, cluster of differentiation (CD)4+ lymphocyte count \<350 cells/µL, a history of an acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months, on the same anti-HIV medications for \<12 weeks or further changes in the number or type of antiretroviral drugs in the regimen could be anticipated in the next 12 weeks (applicable to UK only) * Known serologic status reflecting active hepatitis B or C infection * Active uncontrolled systemic fungal, bacterial, viral, or other infection or a condition predisposing to severe infection