Prospective Study of Cadonilimab With Lenvatinib in Renal Cell Carcinoma

Prior treatment

• 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;
• 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;
• Participating in or having participated in other clinical investigators within 4 weeks prior to the start of the study;
• At risk of bleeding, or coagulation dysfunction, or being treated with thrombolysis;
• 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;

Other illness

• Active or uncontrolled severe infections (≥CTCAE grade 2 infections) requiring systemic antibacterial, antifungal, or antiviral treatment, including tuberculosis.
• Renal failure requires hemodialysis or peritoneal dialysis;
• A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• People with a history of active tuberculosis;
• Failure to control, still need repeated drainage, ascites, pericardial effusion, pleural effusion;
• Patients with severe hypersensitivity after the use of monoclonal antibodies; Known allergy to the active ingredients or excipients of the drug in this study;
• People with a history of severe allergies;
• Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;

Lab values

• 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);
• Have grade ≥2 myocardial ischemia or myocardial infarction, arrhythmia (QTc≥470ms), and grade ≥2 congestive heart failure (New York Heart Association \[NYHA\] grade);
• 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;
• 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;

Other

• Poor patient compliance;
• Patients who have undergone major organ transplants;
• The investigator considers it inappropriate to participate in the clinical trial for any reason;

• Sign written informed consent before enrollment;
• Age ≥18 years old;
• Histological and/or cytological diagnosis of unresectable advanced renal cell carcinoma;
• 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;
• 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.
• Consent to medical treatment;
• Understand and voluntarily sign written informed consent.
• ECOG score: 0 \~ 1;
• 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);
• Have adequate organ function:
• Blood routine: Absolute Neutrophil Count (ANC) 1.5×10\^9/L, Platelet (PLT) ≥70×10\^9/L, Hemoglobin (HGB) ≥80g/L;
• 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.
• Kidney function: serum Creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/mi (using the standard Cockcroft-Gault formula) :
• 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.
• Estimated survival ≥3 months;
• 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.