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

Inclusion Criteria

• Adequate organ and bone marrow function.
• In Part A (dose escalation), participants must be aged ≥ 18 years at the time of signing the informed consent. In Part B (dose optimization/expansion), participants must be at least 15 years of age.
• Histologically confirmed documented diagnosis of r/r cHL based on criteria established by the World Health Organization
• Must provide FFPE baseline tumour tissue to meet the minimum tissue requirement for central MTAP expression determination.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Module 1 (cHL):
• At least 1 radiographically measurable, and/or FDG-avid lymphoma lesion > 1.5 cm.
• Participants must have documented r/r active disease, must have previously received at least 3 prior lines of therapy (including Brentuximab Vedotin and anti-PD-1 therapy) for the treatment of cHL, and must have exhausted all available therapies with demonstrated clinical benefit.

Exclusion Criteria

• 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.