Inclusion Criteria:
1. Age ≥ 18, no gender limitation;
2. Histopathological confirmed RCC, and diagnosed as FH-dRCC by Sanger or NGS sequencing after being included in preliminary IHC screening;
3. The patients incuded must be diagnosed with metastatic RCC or TNM stage IV (according to the 2009 TNM staging system), with distant metastasis confirmed by radiology or pathology.
4. Have not received systemic treatment, including cytokines, targeted drugs, or other experimental drugs, or have received targeted drugs (within the range of 1st-line targeted drugs recommended by NCCN2022 for renal cancer) with single drug treatment for less than 1 month and have completed the washout period. ECOG score ≤ 2;
5. Life expectancy ≥ 3 months;
6. Signed written informed consent form and willing and able to comply with scheduled visits and other requirements of the study；
7. Agree to collect tumor tissue and blood samples required for this study and apply the samples to relevant studies;
8. Adequate organ and bone marrow function: absolute neutrophil count (ANC): ≥1×109/L, platelet count (PLT) ≥50×109/L, hemoglobin content (HGB) ≥80g/L; Liver function: total bilirubin (TBIL) ≤3×normal upper limit (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5×ULN, albumin ≥20g/L; Renal function: serum creatinine (Cr) ≤3×ULN.
Exclusion Criteria:
1. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 antibody, or any other antibodies or drugs specifically targeting co-stimulatory or checkpoint pathways of T cells;
2. Active brain metastasis;
3. Other malignancy with primary site or histological type different from tumors evaluated in this study within 2 years of personal history, except skin basal cell carcinoma, squamous cell carcinoma or adequately treated cervical carcinoma in situ;
4. Underwent major operation (craniotomy, thoracotomy or laparotomy) within 4 weeks of the first dose of study medication or with severe trauma;
5. Received systemic treatment with corticosteroids (\> 10mg daily prednisone equivalent) or other immunosuppressive medications within 4 weeks of first dose. Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
6. Known or suspected active autoimmune disease (congenital or acquired), including interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. Patients with type I diabetes, hypothyroidism that only requires systemic treatment (including vitiligo, psoriasis, alopecia, etc.), or conditions that are not expected to recur in the absence of external triggers are eligible to participate in this study; Known history of allogeneic organ (except corneal transplantation) or allogeneic hemopoietic stem cell transplantation;
7. Known allergy or hypersensitivity to any monoclonal antibodies or any components used in their preparation;
8. Uncontrolled concomitant disease, including but not limited to:
1. Active or poorly controlled severe infection;
2. Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
3. Known acute or chronic active hepatitis B infection (HBsAg positive and HBV DNA\>1\*103/ml), or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA\>15IU/ml);
4. Active tuberculosis;
9. Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia;
10. Poorly controlled arterial hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg) with standard treatment;
11. Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke and transient ischemic attack, within 6 months of enrollment;
12. Diseases that require anticoagulant treatment with warfarin (coumarin);
13. Poorly controlled hypercalcemia (Ca2+ \> 1.5mmol/L, or serum calcium \> 12mg/dL, or corrected serum calcium \> ULN), or symptomatic hypercalcemia requiring bisphosphate treatment;
14. Other acute or chronic diseases, mental illness, or abnormal laboratory test results that may lead to the following outcomes: increase the risk of participating in study or study drug administration, or interfere with the interpretation of the study results and considered by investigator as "NOT" eligible to participate in this study;
15. Women who are pregnant or nursing.
