A Study of Cadonilimab（AK104） Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma

Inclusion Criteria: Provide written informed consent/assent for the trial. Be ≥18 and ≤ 75 years of age on day of signing informed consent. 3）Have histologically or cytologically confirmed diagnosis of RCC with advanced/metastatic disease with clear cell component. 4)Have previous immunotherapy combined treatment progression（ only second line systemic therapy for advanced RCC included) 5)Have measurable disease per RECIST 1.1 as assessed by the investigator /site radiologist. 6)Have estimated life expectancy of at least 3 months. 7)Have ECOG PS 0-1. 8)Hematology: i. absolute neutrophil count (ANC) ≥ 1.5 × 109/L ; ii. platelets ≥ 100 × 109/L ; iii. hemoglobin ≥ 90 g/L. 9)Renal: i. calculated creatinine clearance * (CrCl) ≥ 60 mL/min; * CrCl will be calculated using the Cockcroft-Gault formula CrCL (mL/min) = {(140-age) × body weight (kg) × F }/(SCr (mg/dL) × 72) ii. urine protein < 2 + or 24-hour urine protein must be < 2.0 g. 10)Hepatic: i. serum total bilirubin (TBil) ≤ 1.5 × ULN; ii. AST and ALT ≤ 3 × ULN, ≤ 5 × ULN with liver metastasis; iii. serum albumin (ALB) ≥ 28 g/L. 11)Coagulation function: i. international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. Exclusion Criteria: Has history of allergies to monoclonal antibodies, any components of cadonilimab and lenvatinib Has a known additional malignancy that has progressed or has required active treatment. Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or carcinoma in situ are not excluded. Has prior Dual immunotherapy treatment (any anti-PD-1/PD-L1 combined with anti-CLTA-4 ). Has Uncontrolled clinical symptoms or diseases of the heart Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days （prednisone>10 mg/day or equivalent dose) Has active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Subjects with diabetes type I, vitiligo, psoriasis, hypo-or hyperthyroid disease not requiring immunosuppressive treatment are eligible. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. Has an active tuberculosis and syphilitic infection. Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV antibodies). Has known active Hepatitis B (e.g., Hepatitis B surface antigen [HBsAg] reactive and HBV-DNA>500 IU/ml) or Hepatitis C virus (e.g., HCV RNA [qualitative] is detected). Has never recovered from previous anti-tumor treatment toxicity Has active bleeding disorder or other history of significant bleeding episodes . drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results; Is pregnant or breastfeeding, or expecting to conceive children duration of the trial. -