SYH2095 for Advanced Malignant Tumors: Phase I Study

Presence of known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Participants with prior locoregional treatment for brain metastases may be enrolled only if medically stable for ≥ 4 weeks prior to the first dose. Medically stable is defined as the following conditions: no clinical symptoms attributable to CNS metastases within 4 weeks prior to the first dose (e.g., progressive or new neurological deficit, epileptic seizure, increased intracranial pressure, vomiting, papilledema, or headache); no evidence of CNS neoplasm relapse/progression on imaging assessments within 4 weeks prior to the first dose; no glucocorticoid therapy (>10 mg/day prednisone or equivalent) for ≥4 weeks prior to the first dose;

Participants with uncontrolled third interstitial effusions (e.g., pericardial effusion, pleural effusion, ascites) that cannot be controlled by repeated drainage or other interventions, and who are not suitable for enrollment by the investigator;

Participants with history of severe cardiovascular disease within 6 months prior to the first dose, including any of the following: (1) Congestive heart failure (New York Heart Association (NYHA) class > grade Ⅱ); (2) Severe/unstable angina, or new-onset angina pectoris within 3 months before the first dose; (3) Participants with myocardial ischaemia requiring long-term pharmacologic control, or heart failure (NYHA class Ⅲ-Ⅳ); (4) History of acute myocardial infarction; (5) Any grade ≥2 supraventricular or ventricular arrhythmia requiring treatment or intervention; (6) History of atrial fibrillation, coronary/peripheral artery bypass grafting, or transient ischaemic attack (TIA) with cerebrovascular symptoms; (7) Uncontrolled hypertension at screening (despite pharmacotherapy: diastolic blood pressure ≥ 100 mmHg and/or systolic blood pressure ≥ 160 mmHg);(8) QTcF≥ 470 ms on 12-lead (ECGs) performed in triplicate;

Participants with factors affecting oral administration (e.g., dysphagia, intestinal obstruction); or active gastrointestinal diseases or other conditions that may significantly alter drug absorption, distribution, metabolism, or excretion (including active inflammatory bowel disease, chronic diarrhea, frequent vomiting, enterocolitis, etc.);