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