Safety and Efficacy of Yiwoxidan Anti (AK112) Monotherapy in Patients With Metastatic Renal Clear Cell Carcinoma Who Are Intolerant to TKI Treatment: a Prospective, Single Arm, Phase II Clinical Study

Inclusion criteria

• Age between 18 and 75 years, inclusive.
• Histologically confirmed diagnosis of clear cell renal cell carcinoma (ccRCC).
• Metastatic disease with at least one measurable lesion according to RECIST v1.1 criteria.
• No prior systemic therapy for advanced or metastatic ccRCC.
• ECOG Performance Status of 0 or 1.
• Expected survival ≥12 weeks.
• Adequate organ function:

• Hemoglobin ≥9 g/dL
• Absolute neutrophil count ≥1.5 × 10⁹/L
• Platelets ≥100 × 10⁹/L
• Total bilirubin ≤1.5 × ULN
• AST/ALT ≤2.5 × ULN (≤5.0 × ULN if liver metastases present)
• Serum creatinine ≤1.5 × ULN or eGFR ≥60 mL/min/1.73m²
• INR ≤1.5 or aPTT within normal limits
• Female patients of childbearing potential must have a negative pregnancy test at screening and agree to use effective contraception during the study and for 12 weeks after last dose.
• Willing and able to provide written informed consent.

Exclusion criteria

• 1. Non-clear cell histology or mixed histology with non-clear cell component >25%.

• Prior treatment with PD-1/PD-L1 inhibitors, VEGF/VEGFR inhibitors, or other immune checkpoint inhibitors.

• Active autoimmune disease requiring systemic immunosuppressive therapy. 4. Uncontrolled hypertension (systolic BP >150 mmHg or diastolic BP >100 mmHg despite medication).

• Significant cardiovascular disease including unstable angina, myocardial infarction, or congestive heart failure (NYHA Class III-IV) within 6 months.

• Symptomatic central nervous system metastases or spinal cord compression. 7. Active infection including HBV, HCV, HIV, or active tuberculosis. 8. Known hypersensitivity to AK112 or its excipients. 9. Pregnancy or breastfeeding. 10. Any condition that may interfere with the interpretation of study results or pose an undue risk to the participant, as determined by the investigator.