Status:

RECRUITING

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

Lead Sponsor:

AstraZeneca

Conditions:

Lymphoma

Non-Hodgkin

Eligibility:

All Genders

15+ years

Phase:

PHASE1

PHASE2

Brief 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 p...

Detailed Description

This is a FTiH modular, Phase I/II, open-label, multicentre, dose escalation and expansion study in participants with r/r haematologic malignancies. The study is designed to evaluate the safety, toler...

Eligibility Criteria

Inclusion

  • 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.

Exclusion

    Key Trial Info

    Start Date :

    January 23 2024

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    May 8 2026

    Estimated Enrollment :

    110 Patients enrolled

    Trial Details

    Trial ID

    NCT06137144

    Start Date

    January 23 2024

    End Date

    May 8 2026

    Last Update

    June 12 2025

    Active Locations (20)

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    Page 1 of 5 (20 locations)

    1

    Research Site

    Miami, Florida, United States, 33136

    2

    Research Site

    Atlanta, Georgia, United States, 30322

    3

    Research Site

    Boston, Massachusetts, United States, 02215

    4

    Research Site

    Philadelphia, Pennsylvania, United States, 19104