Inclusion Criteria:
1. Signed informed consent
2. Age 18 to 85 years
3. Histologically or cytologically confirmed metastatic or unresectable nccRCC
4. At least one measurable lesion per RECIST v1.1
5. No prior systemic therapy for advanced disease
6. ECOG performance status 0-1
7. Adequate organ function
8. Life expectancy ≥3 months
Exclusion Criteria:
1. History of allergy to any component of serplulimab or fruquintinib.
2. History of or concurrent malignancy, excluding skin basal cell carcinoma, cervical carcinoma in situ, and papillary thyroid carcinoma, that has not been cured for more than 5 years or has active cancer.
3. Uncontrolled cardiac symptoms or diseases, including NYHA class II or higher heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant atrial or ventricular arrhythmias requiring intervention.
4. Previous treatment with PD-1, PD-L1, or CTLA-4 antibodies; investigational drugs within 4 weeks before the first dose; enrollment in another interventional clinical trial; systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 2 weeks before the first dose, subject to protocol-specified exceptions; antitumor or live vaccines within 4 weeks; or major surgery or serious trauma within 4 weeks.
5. Toxicity from previous anticancer therapy not recovered to CTCAE grade 1 or lower, excluding alopecia and residual neurotoxicity related to previous platinum therapy, or otherwise not meeting the eligibility criteria.
6. Serious infection (CTCAE grade \>2) within 4 weeks before the first dose, including severe pneumonia, sepsis requiring hospitalization, infection-related complications, active pulmonary inflammation on baseline imaging, symptoms or signs of infection, or need for oral or intravenous antibiotics.
7. Active autoimmune disease or history of autoimmune disease, subject to the protocol-specified exceptions for stable thyroid replacement, type 1 diabetes on stable insulin, vitiligo, and childhood asthma or allergy in remission.
8. History of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency, organ transplantation, or allogeneic bone marrow transplantation.
9. History of interstitial lung disease, excluding radiation pneumonitis not treated with steroids, or history of noninfectious pneumonia.
10. Evidence of active tuberculosis infection, active tuberculosis within 1 year before screening, or inadequately treated tuberculosis more than 1 year before screening.
11. Active hepatitis B or hepatitis C as defined in the protocol; eligible patients with controlled hepatitis B must receive protocol-specified antiviral therapy.
12. Known history of psychotropic substance abuse, alcoholism, or drug use.
13. Pregnant or lactating women.
14. Other factors that, in the investigator's judgment, could require withdrawal or compromise patient safety or data collection, including serious concomitant illness, significant laboratory abnormalities, or family or social factors.
15. Severe active bleeding, active peptic ulcers, unhealed gastrointestinal perforations, or gastrointestinal fistulas.
