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

Principle Inclusion Criteria:

• Participant must be at least 18 years of age or the legal age of consent in thejurisdiction 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 tissuerequirement for central MTAP deficiency testing.

• Participants must have received and progressed, are refractory or are intolerant tostandard therapy for the specific tumor type. All participants are required to havehad 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 moreexons of the MTAP gene in tumor tissue AND/OR loss of MTAP expression in the tumortissue.

• 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 ResponseEvaluation 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 regulationsregarding the methods of contraception for those participating in clinical studies.

Principle Exclusion Criteria:

• Spinal cord compression or symptomatic and unstable brain metastases orleptomeningeal 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 infarctionwithin 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 6months, 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 oraltherapy.

• History of another primary malignancy.

• Unresolved toxicities from prior anti-cancer therapy, except alopecia andneuropathy.

• Prior treatment with a protein arginine methyltransferase 5 (PRMT5) inhibitor .