PAS-004 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •1. Participation in another therapeutic clinical trial within 3 weeks of enrollment.
• •2. Having received chemotherapy, radiotherapy, major surgery, targeted therapy, immunotherapy, or other antitumor treatment within 21 days of enrollment or five half-lives of the administered therapy, whichever occurs first.
• •3. Known or active central nervous system metastases.
• •1. Patients with untreated brain metastases ≤ 30 mm that are asymptomatic, do not have significant edema, and do not require steroids or anti-seizure medications are eligible after discussion with the Medical Monitor.
• •2. Patients with previously treated brain metastases may participate provided they are stable after treatment and without evidence of progression by imaging for at least 4 weeks prior to the first dose of IP administration and are not using corticosteroids for at least 7 days prior to IP administration.
• •3. Patients with confirmed leptomeningeal disease are to be excluded.
• •4. Unresolved toxicity from prior antitumor therapy defined as AEs \> Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for alopecia; neurotoxicity AEs of patients who have received prior chemotherapy needs to be restored to Grade 2 or below. Patients with ≥ Grade 3 bleeding within 4 weeks of first study treatment dose should be excluded.
• •5. Taken a medication that is a strong cytochrome P450 (CYP3A) inhibitor or inducer within 14 days of initiation of study therapy dosing.
• •6. Taken a known corrected QT (QTc) interval prolongating medication within 7 days of initiation or longer if the half-life of the QTc prolonging medication is such that the drug is not cleared from the body within 7 days (5 half-lives) of initiation of study therapy dosing.
• •7. Active dysphagia, digestive system disease, malabsorption syndrome, or other conditions affecting PAS-004 absorption.
• •8. Previous or current retinal vein stenosis, retinal detachment, central retinal vein occlusion, or currently active glaucoma.
• •9. Active interstitial pneumonia, including clinically significant radiation pneumonitis.
• •10. Impaired cardiac function or cardiac disease as indicated by:
• •1. Average QTc interval \> 470 ms as calculated according to the QTc formula of the instrument at the research center where electrocardiogram (ECG) measurements are performed.
• •2. Grade ≥ 3 congestive heart failure per New York Heart Association (NYHA) guidelines.
• •3. Clinically significant arrhythmias, including but not limited to, complete left bundle branch conduction abnormalities and 2nd degree atrioventricular block.
• •11. Pregnant or lactating female patients.
• •12. Known allergy or hypersensitivity to the investigational product (IP), including excipients, or history of severe adverse reaction to any drug, or sensitivity to components of the IP.
• •13. Clinically active bacterial, fungal, or viral infections, hepatitis B (hepatitis B virus surface antigen positive and hepatitis B virus DNA over 1000 IU/ml) or hepatitis C (hepatitis C virus RNA positive), human immunodeficiency virus infection (HIV positive).