Milaberon in Advanced Solid Tumors: an Open, Multicenter Clinical Study

Exclusion Criteria

• •Received the following treatment within 4 weeks before treatment: radiotherapy of tumor, major surgical operation or wound has not been completely healed, β3 adrenoceptor agonist and corresponding clinical research drugs;
• •those who have contraindications to Miraberon: those who are allergic to Miraberon or any of its excipients;
• •Active malignant tumors in the past 3 years, except for tumors participating in the study and local tumors that have been cured, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, etc;
• •symptomatic brain or meningeal metastases; Severe infection (such as intravenous infusion of antibiotics, antifungals, or antivirals) within 4 weeks before treatment, or fever of unknown origin\> 38.5°C during screening/first dose;
• •have high blood pressure that cannot be well controlled by antihypertensive drug therapy (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
• •Within 3 months before treatment, there were obvious clinical bleeding symptoms or obvious bleeding tendency (bleeding\> 30 mL within 3 months, hematemesis, black stool, hematochezia), hemoptysis (fresh blood\> 5 mL within 4 weeks), etc. or a venous/venous thrombotic event within 6 months prior to treatment, such as a cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; or the need for long-term anticoagulant therapy with warfarin or heparin, or the need for long-term antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day);
• •The tumor is found to invade large vascular structures during screening, such as pulmonary artery, superior vena cava or inferior vena cava, and the researchers judge that there is a greater risk of bleeding;
• •Active heart disease, including myocardial infarction, severe/unstable angina pectoris, 6 months before treatment. Echocardiography left ventricular ejection fraction \<50%, arrhythmia poorly controlled;
• •Uncontrollable pleural effusion, pericardial effusion or ascites requiring frequent drainage after appropriate intervention;
• •Presence of any active autoimmune disease or history of autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial pneumonia, pulmonary fibrosis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroid function progression, decreased thyroid function; Note:(1) Subjects whose thyroid function can only be controlled by hormone replacement therapy can be included;(2) Subjects with skin diseases that do not require systemic treatment, such as vitiligo, psoriasis, alopecia, type 1 diabetes, or childhood asthma has been completely resolved, and no intervention can be included after adulthood;(3) Patients with asthma who require medical intervention with bronchodilators cannot be included;
• •received treatment with live attenuated vaccine within 28 days prior to the first administration of the study drug;
• •The patient has a known history of psychotropic substance abuse, alcohol abuse or drug abuse; a history of definite neurological or psychiatric disorders, including epilepsy or dementia
• •tuberculosis infection history;
• •known human immunodeficiency virus (HIV) infection;
• •Known history of clinically significant liver disease, including viral hepatitis \[Known hepatitis B virus (HBV) carriers must exclude active HBV infection, I .e., HBV DNA positive (\>1 × 104 copies/mL or\> 2000 IU/mL);
• •Known hepatitis C virus infection (HCV) and HCV RNA positive (\>1 x 103 copies/mL), or other hepatitis, cirrhosis\];
• •Patients with renal injury: GFR\<30 mL/min 1.73m2 or patients requiring hemodialysis
• •any other medical condition, clinically significant metabolic, physical, or laboratory abnormality, which, in the investigator's judgment, would reasonably suspect that the patient has a disease or condition that is not appropriate for the study drug (e. g., having seizures requiring treatment, bladder outlet obstruction, anxiety), or would interfere with the interpretation of the study results, or place the patient in a high-risk situation, or patients considered by the investigator to be unsuitable for inclusion.