Perioperative TORIPALIMAB Plus LENVATINIB in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PLUTO)

Inclusion Criteria:

• Have fully understood and voluntarily signed the informed consent Form (ICF);

• Age: 18-80 years old (at the time of signing the informed consent); Both male andfemale; ECOG PS score: 0-1;

• RCC with clear cell component confirmed by histology or cytopathology, includinglocally advanced RCC with clear cell component;

• ECOG 0-1 points

• T1b-T2bN0M0, T3a-4N0M0, TanyN1M0 or M1RCC diagnosed by imaging at initial diagnosis:

1. Cohort 1: T1b-T2bN0M0 RCC;

2. Cohort 2: T3a-4N0M0 or TanyN1M0 RCC;

3. Cohort 3: M1 RCC undergoing cytoreductive nephrectomy.

• Radical nephrectomy or partial nephrectomy or renal tumor enucleation was decidedafter the clinician made the treatment plan and communicated with the patient;

• Willingness and ability to comply with planned visits, therapeutic laboratorytesting, and other procedures.

Exclusion Criteria:

• Signs of tumor metastasis involving the central nervous system;

• History of malignant tumors other than the study disease within the previous 5years, with the exception of malignant tumors that can be expected to be cured withtreatment (including but not limited to adequately treated thyroid cancer, carcinomain situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma insitu of the breast treated with radical surgery);

• Prior to participating in the study, patients had received other systemic treatmentdrugs, including targeted drugs, immunotherapy drugs and their combination regimens,or local anti-tumor therapy, or received investigational drugs or device therapy;

• Underwent major surgery (judged by the investigator) within 4 weeks before the firsttrial dose, were recovering, or were 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 limitedto:

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 qualityof 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 stemcell transplantation or long-term corticosteroid therapy. Patients with thyroid,suprarenal or hypopituitarism that could be controlled only with hormone replacementtherapy, type 1 diabetes mellitus, psoriasis or vitiligo without systemic treatment,etc., were eligible to participate in the study.

• Non-resolution of toxicity after previous antineoplastic therapy, i.e., resolutionto baseline, NCI-CTCAE 5.0 grade 0-1 (excluding alopecia), or inclusion/exclusioncriteria. Irreversible toxicities (e.g., hearing loss) that would not reasonably beexpected to be exacerbated by the study drug can be included in the study;

• Known history of clinically significant liver disease, including active viralhepatitis (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, clinicallysignificant moderate to severe cirrhosis;

• Patients with uncontrolled third space effusion requiring repeated drainage, such aspleural effusion, ascites, pericardial effusion, etc. (Patients who do not needdrainage of effusion or stop drainage for 3 days without significant increase ineffusion can be enrolled);

• Receiving a systemic corticosteroid (prednisone > 10mg/ day or equivalent) or otherimmunosuppressive 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 (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg);

2. Unstable angina pectoris or myocardial infarction, coronary artery bypassgrafting 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 HeartAssociation (NYHA) classification); Degree Ⅱ or above heart block; Leftventricular 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 notlimited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory boweldisease, etc.;

• Renal failure requiring hemodialysis or peritoneal dialysis;

• Patients with a history of immunodeficiency, including HIV positive patients, otheracquired immunodeficiency diseases, congenital immunodeficiency diseases, or organtransplantation history;

• History of live attenuated vaccine inoculation within 4 weeks before the first studydrug or the expected vaccination during the study period;

• History of psychiatric drug abuse and can not quit or have a history of mentaldisorders;

• The presence of any other severe, acute or chronic medical disease or mental illnessor laboratory abnormality, as judged by the investigator, that may increase the riskassociated with participation in the study or that may interfere with theinterpretation of the results of the study.