AZD3470 as Monotherapy and in Combination With Anticancer Agents in Participants With Relapsed/Refractory Haematologic Malignancies.

Exclusion Criteria19

• Any significant laboratory finding or any severe and uncontrolled medical condition.
• Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord compression.
• Serologic active HBV or HCV infection.
• Known to have tested positive for HIV.
• Active gastrointestinal disease or other condition that will interfere with oral therapy.
• Any of the following cardiac criteria:
• Mean resting QTcF \> 470 msec or clinically important abnormalities in rhythm (ventricular arrhythmias and uncontrolled atrial fibrillation)
• Factors that increase the risk of QTc prolongation or risk of arrhythmic events
• Cardiac procedures or conditions within the last 6 months: Coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or heart valve intervention vascular stent implantation, acute coronary syndrome / myocardial infarction, uncontrolled angina pectoris, use of therapeutic anti-coagulation for treatment of active thromboembolic events.
• Severe valvular heart disease
• Congestive heart failure Grade II to Grade IV
• Prior or current cardiomyopathy
• Uncontrolled hypertension
• Brain perfusion problems such as haemorrhagic or thrombotic stroke (including transient ischemic attacks)
• Unresolved non-haematological toxicities of Grade \> 1 from prior anticancer therapy (excluding peripheral neuropathy, vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy, and asymptomatic laboratory abnormalities), unless immune-mediated.
• History of another primary malignancy.
• History of significant haemoptysis or haemorrhage within 4 weeks of the first dose of study treatment.
• Requires ongoing immunosuppressive therapy, including systemic corticosteroids.
• Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.