A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors

NCT ID: NCT06130553

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

234 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-18

Study Completion Date

2026-02-26

Brief Summary

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This is a first time in human (FTiH) Phase I/IIa, open-label, multi-centre study of AZD3470 in participants with advanced or metastatic solid tumors with MTAP deficiency. The study consists of several study modules, evaluating the safety, tolerability, pharmacokinetic (PK), pharmacodynamics, and preliminary efficacy of AZD3470 as monotherapy or in combination with other anti-cancer agents.

Detailed Description

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This first time in human, open-label, multi-centre study of AZD3470 in participants with advanced or metastatic solid tumors with MTAP deficiency follows a modular design. Module 1 Part A will include the dose escalation cohorts. Part B will include the dose optimization and expansion cohorts. New modules for combination treatments may be added in the future based on emerging data.

Conditions

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Advanced Solid Tumors That Are MTAP Deficient

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

This is a FTiH (first time in human), modular Phase I/IIa, open-label, multi-centre study of AZD3470, in participants with MTAP deficient advanced/metastatic solid tumors. The study consists of individual modules, each evaluating safety and tolerability of AZD3470 dosed as a monotherapy and in combination with specific treatments. Module 1 describes AZD3470 monotherapy, and will have at least two parts. Part A will include the dose escalation cohorts. Part B will include the dose optimization and expansion cohorts.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AZD3470 Monotherapy

Part A dose escalation and back-fill cohorts and Part B dose optimization and expansion cohorts of varying doses of AZD3470

Group Type EXPERIMENTAL

AZD3470

Intervention Type DRUG

AZD3470 is a novel, potent and selective, second-generation, MTAP-selective, inhibitor of PRMT5.

Interventions

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AZD3470

AZD3470 is a novel, potent and selective, second-generation, MTAP-selective, inhibitor of PRMT5.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participant must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the ICF.
* Willing to provide archival and/or baseline tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing.
* Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumor type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting.
* MTAP deficient tumors defined as evidence of homozygous deletion of one or more exons of the MTAP gene in tumor tissue AND/OR loss of MTAP expression in the tumor tissue.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* A minimum life expectance of 12 weeks in the opinion of the Investigator.
* Participants must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Adequate organ and bone marrow reserve function.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria

* Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease or primary malignancies of the central nervous system.
* Allogeneic organ transplantation.
* Any significant laboratory finding or any severe and uncontrolled medical condition.
* Any of the following cardiac criteria:
* LVEF ≤ 50%
* prior or current cardiomyopathy
* clinically active cardiovascular disease, or a history of myocardial infarction within the last 6 months
* uncontrolled angina or acute coronary syndrome within 6 months
* severe valvular heart disease
* uncontrolled hypertension
* risk of brain perfusion problems. Stroke or transient ischemic attack in the last 6 months, undergone coronary artery bypass graft, angioplasty or vascular stent
* chronic heart failure
* factors that increase the risk of QTc prolongation or risk of arrhythmic events
* Mean resting QTcF \> 470 msec or any clinically important abnormalities in rhythm
* Use of therapeutic anti-coagulation for treatment of acute thromboembolic events.
* Serologic active hepatitis B or C infection.
* Known to have tested positive for Human immunodeficiency virus (HIV).
* Confirmed or suspected ILD/pneumonitis or history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen
* Active gastrointestinal disease or other condition that would interfere with oral therapy.
* History of another primary malignancy.
* Unresolved toxicities from prior anti-cancer therapy, except alopecia and neuropathy.
* Prior treatment with a protein arginine methyltransferase 5 (PRMT5) inhibitor .
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

San Francisco, California, United States

Site Status RECRUITING

Research Site

West Hollywood, California, United States

Site Status WITHDRAWN

Research Site

New Haven, Connecticut, United States

Site Status RECRUITING

Research Site

Baltimore, Maryland, United States

Site Status RECRUITING

Research Site

Portland, Oregon, United States

Site Status RECRUITING

Research Site

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Research Site

Providence, Rhode Island, United States

Site Status RECRUITING

Research Site

Fairfax, Virginia, United States

Site Status RECRUITING

Research Site

Melbourne, , Australia

Site Status RECRUITING

Research Site

Beijing, , China

Site Status RECRUITING

Research Site

Chengdu, , China

Site Status RECRUITING

Research Site

Shanghai, , China

Site Status RECRUITING

Research Site

Villejuif, , France

Site Status NOT_YET_RECRUITING

Research Site

Chūōku, , Japan

Site Status RECRUITING

Research Site

Kashiwa, , Japan

Site Status RECRUITING

Research Site

Amsterdam, , Netherlands

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status RECRUITING

Research Site

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Australia China France Japan Netherlands South Korea Spain

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

Other Identifiers

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165618

Identifier Type: REGISTRY

Identifier Source: secondary_id

D9970C00001

Identifier Type: -

Identifier Source: org_study_id