Fruquintinib Plus Serplulimab as First-Line Therapy for Metastatic Non-Clear Cell Renal Cell Carcinoma

Prior treatment

• 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.
• 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.
• 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.
• 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.
• History of interstitial lung disease, excluding radiation pneumonitis not treated with steroids, or history of noninfectious pneumonia.

Other illness

• History of allergy to any component of serplulimab or fruquintinib.
• 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.
• 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.
• History of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency, organ transplantation, or allogeneic bone marrow transplantation.
• Evidence of active tuberculosis infection, active tuberculosis within 1 year before screening, or inadequately treated tuberculosis more than 1 year before screening.
• Active hepatitis B or hepatitis C as defined in the protocol; eligible patients with controlled hepatitis B must receive protocol-specified antiviral therapy.
• Known history of psychotropic substance abuse, alcoholism, or drug use.
• Severe active bleeding, active peptic ulcers, unhealed gastrointestinal perforations, or gastrointestinal fistulas.

Lab values

• 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.

Other

• Pregnant or lactating women.

• Signed informed consent
• Age 18 to 85 years
• Histologically or cytologically confirmed metastatic or unresectable nccRCC
• At least one measurable lesion per RECIST v1.1
• No prior systemic therapy for advanced disease
• ECOG performance status 0-1
• Adequate organ function
• Life expectancy ≥3 months