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, 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
• 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