A Study of TY-1091 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •1. For NSCLC patients, a targetable mutation in EGFR or MET, targetable rearrangement involving ALK, ROS1 or NTRK1-3.
• •2. History of other previous cancer (except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected), requiring therapy within the previous 5 years.
• •3. For MTC patients, clinically significant involvement in the trachea, esophagus or complete encasement of great vessels (e.g., aorta or pulmonary artery) that in the opinion of the Investigator, could result in life-threatening complications due to rapid tumor regression.
• •4. Symptomatic primary central nervous system (CNS) tumor or metastases; symptomatic leptomeningeal carcinomatosis; untreated spinal cord compression.
• •5. Cardiovascular and cerebrovascular diseases/symptoms/indications meeting any of the following conditions:
• •Mean resting corrected QT interval (electrocardiogram interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) ≥470 msec obtained from 3 electrocardiograms; Any clinically significant resting ECG abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, second and third degree heart block, PR interval \> 250 ms; Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong QT interval; Left ventricular ejection fraction (LVEF) \< 50%; Patients with a previous history of decreased myocardial contractility who experienced relevant symptoms within 6 months prior to study drug administration: such as chronic congestive heart failure, pulmonary edema or decreased cardiac ejection fraction; Patients with a history of acute or chronic cardiovascular and cerebrovascular diseases who had relevant symptoms within 6 months prior to study drug administration: such as myocardial infarction, severe or unstable angina, cerebral infarction, cerebral hemorrhage or transient ischemic attack.
• •6. Patients who have received treatment within 14 days prior to the first dose or need to continue treatment with strong CYP3A4 inducers/strong inhibitors, CYP3A4/CYP2C9/CYP2C19 sensitive substrate with a narrow treatment window or strong p-glycoprotein inhibitors.
• •7. Systemic anti-tumor treatment such as standard chemotherapy, biological therapy and immunological drug therapy within 28 days prior to the first dose; targeted therapy within 14 days or 5 half-lives of the first dose (calculated as a long time); anti-tumor traditional Chinese traditional medicine treatment within 7 days prior to the first dose.