Prospective Study of Cadonilimab With Lenvatinib in Renal Cell Carcinoma

This is a prospective, open, multi-cohort phase II study The study included a screening period (participants signed informed consent no more than 28 days before the first treatment in the study), a treatment period (treatment termination was defined as termination of treatment for any reason, such as imaging confirmation of disease progression, failure to tolerate adverse effects after dose adjustment, or early withdrawal for any reason), and a follow-up period (including end-of-treatment visits, safety visits, and survival follow-up). Screening period: Participants are required to undergo a screening period within 28 days prior to the study's first treatment to determine eligibility. Duration of treatment: Patients were treated with Cadonilimab in combination with lenvatinib until disease progression or intolerable toxicity developed. Every 3 weeks was a dosing cycle, and every 6 weeks was a treatment assessment. Follow-up period: The safety follow-up period began after the last study treatment, and was followed up once on the 30th day (±7 days). Subjects should go to the research center for the examination of vital signs, physical examination, laboratory examination and other protocol requirements, and evaluate AE, concomitant medication and concomitant treatment. After the end of the safety follow-up period, the subjects entered the 1-year survival follow-up period, which was conducted every 3 months. They could be visited by telephone follow-up and other effective ways to collect survival information and follow-up treatment information. Survival follow-up lasted until death, loss of follow-up, withdrawal

Inclusion Criteria: 1. Sign written informed consent before enrollment; 2. Age ≥18 years old; 3. Histological and/or cytological diagnosis of unresectable advanced renal cell carcinoma; 4. Cohort 1: renal clear cell carcinoma, mainly renal clear cell carcinoma, was included. Patients progressed after previous treatment with immune checkpoint inhibitor (ICI), and the number of previous treatment lines was less than 3; 5. Cohort 2: Non-transparent renal cell carcinoma was included. Subjects who had not received systematic treatment before or whose disease progressed after TKI or ICI treatment before could be included, with the number of previous treatment lines ≤3; They mainly included cohort A: papillary cell carcinoma, cohort B: chromophobe cell carcinoma, cohort C: collecting tubuloid carcinoma, cohort D: other types. 6. Consent to medical treatment; 7. Understand and voluntarily sign written informed consent. 8. ECOG score: 0 \~ 1; 9. At least one measurable lesion (according to RECIST criteria, the length of CT scan for non-lymph node lesions ≥10 mm, and the short diameter of CT scan for lymph node lesions ≥15 mm); 10. Have adequate organ function: 11. Blood routine: Absolute Neutrophil Count (ANC) 1.5×10\^9/L, Platelet (PLT) ≥70×10\^9/L, Hemoglobin (HGB) ≥80g/L; 12. Liver function: Serum Total Bilirubin (TBIL) ≤1.5× Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤3×ULN; Serum albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN; After routine liver protection treatment, the patients could meet the above criteria and be stable for at least 1 week. 13. Kidney function: serum Creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/mi (using the standard Cockcroft-Gault formula) : 14. Coagulation function: International Normalized Ratio (INR) ≤1.5 /PT≤1.5×ULN, aPTT≤1.5×ULN; If the subject is receiving anticoagulant therapy, as long as PT and INR are within the prescribed range of anticoagulants. 15. Estimated survival ≥3 months; 16. Use of a medically approved contraceptive method is required during the study treatment period and for at least 120 days after the end of the study, and sperm donation to another person or cryopreservation for fertilization and reproduction is not permitted during this period. Ability to adhere to research visit schedules and other protocol requirements. Exclusion Criteria: 1. Poor patient compliance; 2. Subjects with any severe and/or uncontrolled disease. Includes: Poor blood pressure control (systolic ≥150mmHg or diastolic ≥100mmHg); Poor diabetes control (fasting blood glucose \[FBG\] \> 10mmol/L); 3. Have grade ≥2 myocardial ischemia or myocardial infarction, arrhythmia (QTc≥470ms), and grade ≥2 congestive heart failure (New York Heart Association \[NYHA\] grade); 4. Active or uncontrolled severe infections (≥CTCAE grade 2 infections) requiring systemic antibacterial, antifungal, or antiviral treatment, including tuberculosis. 5. Active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B reference: HBV DNA≥2000 IU/ml or ≥104 copy number /ml; Hepatitis C reference: HCV RNA≥2000 IU/ml or ≥104 copy number /ml; After nucleotide antiviral therapy, those who are lower than the above criteria can be included in the group); Chronic hepatitis B virus carriers, HBV DNA \< 104 IU/ml, must also receive antiviral therapy during the trial to be enrolled; 6. Renal failure requires hemodialysis or peritoneal dialysis; 7. A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 8. Active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to the initiation of study treatment, except for alternative therapies (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency); Are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy. Dose \> 10mg/ day of prednisone or other equivalent hormone and within 2 weeks of initial administration and continued use; 9. People with a history of active tuberculosis; 10. Failure to control, still need repeated drainage, ascites, pericardial effusion, pleural effusion; 11. Patients who have undergone major organ transplants; 12. Study participants who received major surgical treatment, open biopsy, or significant traumatic injury within 28 days before the start of treatment; Or have a wound or fracture that has not healed for a long time; 13. Patients with severe hypersensitivity after the use of monoclonal antibodies; Known allergy to the active ingredients or excipients of the drug in this study; 14. Participating in or having participated in other clinical investigators within 4 weeks prior to the start of the study; 15. People with a history of severe allergies; 16. At risk of bleeding, or coagulation dysfunction, or being treated with thrombolysis; 17. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders; 18. Subjects with concomitant diseases that, in the judgment of the investigator, seriously endanger the safety of the subjects or affect the completion of the study, or subjects with concomitant diseases that, in the judgment of the investigator, seriously endanger the safety of the subjects or affect the completion of the study, or subjects with concomitant diseases that, in the judgment of the investigator, seriously endanger the safety of the subjects or affect the completion of the study, or subjects with other reasons that are not suitable for enrollment. Have a clear history of neurological and psychiatric disorders, such as dementia, epilepsy, or predisposition to epilepsy; 19. If, in the investigator's judgment, there is a concomitant medical condition (such as serious diabetes, thyroid disease, and mental illness) that seriously endangers the subject's safety or prevents the subject from completing the study, or there is a serious and/or unstable medical, mental or other condition (including abnormal laboratory tests) that affects the patient's safety or prevents the patient from providing informed consent, Or the presence of any psychological, familial, sociological or geographical conditions that affect the study protocol and follow-up plan; 20. The investigator considers it inappropriate to participate in the clinical trial for any reason;