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

Study identifier:D9971C00001

ClinicalTrials.gov identifier:NCT06137144

EudraCT identifier:N/A

CTIS identifier:2023-506747-42-00

Recruiting

Official Title

A Modular Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability, and Efficacy of AZD3470, a PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agent(s) in Participants With Relapsed/Refractory Haematologic Malignancies

Medical condition

Lymphoma, Non-Hodgkin

Phase

Phase 1/2

Healthy volunteers

Study drug

AZD3470

Sex

All

Estimated Enrollment

110

Study type

Interventional

Age

15 Years - 130 Years

Date

Study Start Date: 23 Jan 2024

Estimated Primary Completion Date: 16 Apr 2026

Estimated Study Completion Date: 16 Apr 2026

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Inclusion and exclusion 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:
o Mean resting QTcF > 470 msec or clinically important abnormalities in rhythm (ventricular arrhythmias and uncontrolled atrial fibrillation)
o Factors that increase the risk of QTc prolongation or risk of arrhythmic events
o 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.
o Severe valvular heart disease
o Congestive heart failure Grade II to Grade IV
o Prior or current cardiomyopathy
o Uncontrolled hypertension
o 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.

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Arms	Assigned Interventions
Experimental: Module 1: Part A (Dose Escalation) and Part B (Dose Expansion/Optimization) In Part A, participants with Relapsed/Refractory classical Hodgkin Lymphoma (cHL) will take AZD3470 tablets orally until PD, unacceptable toxicity, or withdrawal of consent. In Part B, adult and adolescent participants with r/r cHL will take AZD3470 tablets orally until PD, unacceptable toxicity, or withdrawal of consent.	Drug: AZD3470 AZD3470 is a novel, potent and selective, secondgeneration, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5.

Arms

Assigned Interventions

Experimental: Module 1: Part A (Dose Escalation) and Part B (Dose Expansion/Optimization)
In Part A, participants with Relapsed/Refractory classical Hodgkin Lymphoma (cHL) will take AZD3470 tablets orally until PD, unacceptable toxicity, or withdrawal of consent. In Part B, adult and adolescent participants with r/r cHL will take AZD3470 tablets orally until PD, unacceptable toxicity, or withdrawal of consent.

Drug: AZD3470
AZD3470 is a novel, potent and selective, secondgeneration, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5.

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]