Perioperative Trial With IO/TKI for Multi-stage Clear Cell Renal Cell Carcinoma

Exclusion Criteria

• •Signs of tumor metastasis involving the central nervous system, or radiological evidence of brain metastasis;
• •History of malignant tumors other than ccRCC within the previous 5 years, with the exception of malignant tumors that can be expected to be cured with treatment (including but not limited to adequately treated thyroid cancer, carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with radical surgery);
• •Prior to participating in the study, patients have received prior immune checkpoint inhibitors, investigational drugs or device therapy;
• •History of undergoing major surgery (judged by the investigator) within 4 weeks before the first trial dose, are recovering, or are unable to undergo baseline puncture;
• •History of severe drug allergy, including but not limited to antibody drugs;
• •Patients with contraindications to immunotherapy restart, including but not limited to:
• •1. Grade 2-4 immune myocarditis;
• •2. Severe grade 4 proteinuria;
• •3. Severe or life-threatening grade 4 immune hepatitis;
• •4. Severe grade 3-4 immune pneumonitis;
• •5. Severe inflammatory arthritis that significantly affects daily life or quality of life;
• •6. Severe neurological toxicity:
• •7. Myasthenia gravis grade 2-4;
• •8. Guillain-Barre syndrome (GBS) or transverse myelitis of any grade;
• •9. Grade 2-4 encephalitis;
• •10. Severe or life-threatening grade 3-4 pancreatitis;
• •11. Severe or life-threatening bullous disease (grade 3-4);
• •12. Severe grade 3-4 uveitis or episcleritis.
• •Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation or long-term corticosteroid therapy.
• •Known history of clinically significant liver disease, including active viral hepatitis (hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HbcAb) positive, HBV DNA\>10000 copies /mL or \>2000 IU/mL; Hepatitis C virus (HCV) antibody positive and HCV RNA positive), or other active hepatitis, clinically significant moderate to severe cirrhosis;
• •Patients with uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (Patients who do not need drainage of effusion or stop drainage for 3 days without significant increase in effusion can be enrolled);
• •Receiving a systemic corticosteroid (prednisone \> 10mg/ day or equivalent) or other immunosuppressive medication within 14 days before the first study medication;
• •Patients with any severe and/or uncontrolled disease, including:
• •1. Hypertension that is not well controlled by antihypertensive medication;
• •2. Unstable angina pectoris or myocardial infarction, coronary artery bypass grafting or stent implantation within 6 months before study medication;
• •3. Grade I or above myocardial ischemia or myocardial infarction, arrhythmia (including QTc≥480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); Degree II or above heart block; Left ventricular ejection fraction (LVEF) \< 50%;
• •4. Poorly controlled diabetes (fasting blood glucose \> 10 mmol/L);
• •5. Patients with urinary protein ≥++ and confirmed 24-hour urinary protein \> 1.0g;
• •6. Severe active or uncontrolled infection.
• •Patients with or suspected to have active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc.;
• •Renal failure requiring hemodialysis or peritoneal dialysis;
• •Patients with a history of immunodeficiency, including HIV positive patients, other acquired immunodeficiency diseases, congenital immunodeficiency diseases, or organ transplantation history;
• •History of live attenuated vaccine inoculation within 4 weeks before the first study drug or the expected vaccination during the study period;
• •History of psychiatric drug abuse and can not quit or have a history of mental disorders;
• •Women who are of childbearing potential. Women of childbearing potential must have a negative serum or urine pregnancy test, and must use appropriate methods of contraception.
• •The presence of any other severe, acute or chronic medical disease or mental illness or laboratory abnormality, as judged by the investigator, that may increase the risk associated with participation in the study or that may interfere with the interpretation of the results of the study.