A study of AZD3470, a PRMT5 inhibitor, in patients with MTAP deficient advanced/metastatic solid tumors - PRIMROSE

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.