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

• Status: Recruiting
• Trial end date: 2026-05-08
• Target enrollment: 0
• Participant gender: All

Summary

This study is designed to evaluate the safety, tolerability, PK and preliminary efficacy following oral administration of AZD3470 as a monotherapy, and in combination with other anticancer agents in participants with haematologic malignancies.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca

Criteria

Inclusion criteria

• 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

• Willing to provide FFPE baseline tumour tissue to meet the minimum tissue requirement for central MTAP expression determination.

• Participants must have documented r/r active disease, must have previously received at least 3 prior lines of therapy for the treatment of cHL, and must have exhausted all available therapies with demonstrated clinical benefit.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Module 1 (cHL):

• At least 1 radiographically measurable, and/or FDG-avid lymphoma lesion > 1.5 cm.

• Adequate organ and bone marrow function

• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

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 toxicity from prior anticancer therapy of Grade > 1, except alopecia.

• 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.