PRIMROSE: This study is assessing a new targeted therapy (called AZD3470) in people with advanced or metastatic solid cancers that are MTAP deficientA Modular Phase I/IIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agents in Patients With Advanced/Metastatic Solid Tumours That Are MTAP Deficient

Exclusion

• Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.
• Allogenic 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 active 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.