Trial Title:
A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors
NCT ID:
NCT06130553
Condition:
Advanced Solid Tumors That Are MTAP Deficient
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
solid tumor
MTAP deficient
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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 purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AZD3470
Description:
AZD3470 is a novel, potent and selective, second-generation, MTAP-selective, inhibitor of
PRMT5.
Arm group label:
AZD3470 Monotherapy
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Principle 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.
Principle 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Site
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
West Hollywood
Zip:
90048
Country:
United States
Status:
Withdrawn
Facility:
Name:
Research Site
Address:
City:
New Haven
Zip:
06510
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Baltimore
Zip:
21231
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Providence
Zip:
02903
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Beijing
Zip:
100142
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Shanghai
Zip:
200433
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Chuo-ku
Zip:
104-0045
Country:
Japan
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Kashiwa
Zip:
227-8577
Country:
Japan
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Amsterdam
Zip:
1066CX
Country:
Netherlands
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Not yet recruiting
Start date:
January 18, 2024
Completion date:
February 26, 2026
Lead sponsor:
Agency:
AstraZeneca
Agency class:
Industry
Source:
AstraZeneca
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06130553
