Phase I Study of WJ47156 Monotherarpy and in Combination With Other Therapy in Advanced Solid Tumors

Who cannot join

• CNS metastasis；
• Pleural effusion, peritoneal effusion or pericardial effusion with clinical symptoms or requiring repeated treatment (e.g., puncture or drainage);
• Unable to swallow tablets, intestinal obstruction, or other factors affecting the administration and gastrointestinal absorption of tablets
• For the combination therapy, patients will not be enrolled in this study if they meet any of the following criteria:
• （1）Imaging findings at screening showing tumor encasement of a major vessel or significant necrosis and cavity, which may lead to a hemorrhagic risk as judged by the investigator; （2）Patients with active autoimmune diseases requiring systemic treatment (e.g., corticosteroids or immunosuppressive drugs) within 2 years prior to the first dose, including but not limited to systemic systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, vasculitis, etc. However, hypothyroidism, hypoadrenalism or hypopituitarism controlled only by hormone replacement therapy, Type I diabetes mellitus not requiring systemic treatment, psoriasis or vitiligo are allowed; （3）Previously treated with anti-PD-1/L1 therapy; （4）History of interstitial lung disease or previous history of non-infectious pneumonia treated with corticosteroids, or evidence of active pneumonia on imaging at screening; （5）Gastrointestinal perforation, fistula, abdominal abscess and ulcerative disease or history of digestive system ulcerative disease within 6 months prior to the first dose (patients with stable ulcer as assessed by the investigator may be considered for enrollment); （6）Presence of serious, unhealed, or open wounds, active ulcers, or untreated fractures; （7）History of gastrointestinal bleeding within 6 months prior to enrollment, or clear tendency of gastrointestinal bleeding (including hemorrhagic risk of severe esophageal-gastric varices, locally active digestive tract ulcerative lesion, and persistent positive fecal occult blood); （8）Clinically significant hemoptysis or tumor bleeding for any reason within one month prior to the first dose; （9）History of obvious bleeding tendency or severe coagulation dysfunction; （10）Severe drug-related adverse events leading to permanent discontinuation of the drug product or bevacizumab or its analogues; （11）Use of antiplatelet therapy or anticoagulant therapy for treatment within 14 days prior to the first dose; （12）Long-term treatment with nonsteroidal anti-inflammatory drugs is permitted for brief periods of time to relieve symptoms such as fever or pain.
• 5. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure > 100 mmHg) or history of hypertensive crisis or hypertensive encephalopathy; 6. Severe cardiovascular disease, including but not limited to, myocardial infarction, severe/unstable angina, congestive heart failure (New York Heart Association [NYHA] class ≥ 2), clinically significant supraventricular or ventricular arrhythmia requiring drug intervention, aortic aneurysm requiring surgical repair, any arterial thrombosis/embolism event, Grade 3 or higher (Common Terminology Criteria for Adverse Events [CTCAE] v5.0) venous thrombosis/embolism event, transient ischemic attack, cerebral vascular accident; Left ventricular ejection fraction (LVEF) < 50% by echocardiography. Corrected QT interval (QTc) > 480 ms (calculated using the Fridericia method; if QTc is abnormal, measure 3 times at an interval of 2 minutes and use the average).