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

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.

Eligibility

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.

Conditions4

Locations5 sites

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