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

AstraZeneca

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Advanced Solid Tumors That Are MTAP Deficient

Treatments

Drug: AZD3470

Study type

Interventional

Funder types

Industry

Identifiers

NCT06130553

165618 (Registry Identifier)

D9970C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment

234 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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 .