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

NCT06130553 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: D9970C00001165618
• Study Type: interventional
• Target: 234
• Locations: 8 countries
• Sites: 20

Brief Summary

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.

Conditions

Advanced Solid Tumors That Are MTAP Deficient

Keywords

solid tumor; MTAP deficient

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Number of participants with AEs and SAEs

  From time of informed consent to 28 days post last dose of AZD3470

• Incidence of dose-limiting toxicities (DLT)

  Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT). DLT is defined as an AE (adverse event) or abnormal laboratory value that occurs during the DLT period (defined as 21 days after start of study intervention) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications and meets any DLT criteria defined in the clinical study protocol

  From first dose of study treatment until the end of Cycle 1 (each cycle is 21 days)

Secondary Outcomes (16)

• Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - ORR (Objective Response Rate)

  From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).

• Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - DoR (Duration of Response)

  From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).

• Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - Best percentage change in tumor size

  From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).

• Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - PFS (Progression Free Survival)

  From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).

• Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - DCR (Disease Control Rate) at 12 weeks

  From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks).

Study Arms (1)

AZD3470 Monotherapy

EXPERIMENTAL

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

Drug: AZD3470

Interventions

AZD3470 DRUG

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

AZD3470 Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (20)

Research Site

San Francisco, California, 94143, United States

RECRUITING

Research Site

West Hollywood, California, 90048, United States

WITHDRAWN

Research Site

New Haven, Connecticut, 06510, United States

RECRUITING

Research Site

Baltimore, Maryland, 21231, United States

RECRUITING

Research Site

Portland, Oregon, 97239, United States

RECRUITING

Research Site

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

RECRUITING

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Beijing, 100142, China

RECRUITING

Research Site

Chengdu, 610041, China

RECRUITING

Research Site

Shanghai, 200433, China

RECRUITING

Research Site

Villejuif, 94805, France

NOT YET RECRUITING

Research Site

Chūōku, 104-0045, Japan

RECRUITING

Research Site

Kashiwa, 227-8577, Japan

RECRUITING

Research Site

Amsterdam, 1066CX, Netherlands

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Barcelona, 8035, Spain

RECRUITING

Research Site

Madrid, 28027, Spain

RECRUITING

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 19, 2023
• First Posted: November 14, 2023
• Study Start: January 18, 2024
• Primary Completion: February 26, 2026
• Study Completion: February 26, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

FR (1); US (8); ES (2); AU (1); JP (2); CN (3); NL (1); KR (2)