A Study of IBR854 Combined With Pazopanib Versus Pazopanib in Advanced Renal Cell Carcinoma

Exclusion Criteria

• •1. Documented central nervous system metastases.
• •2. Received prior antineoplastic therapy (including chemotherapy, biologic therapy, immunotherapy, or Chinese traditional medicines with antitumor indications) before the first dose of study treatment.
• •3. Has received major surgery (grade 3 or 4 as defined in the Measures for the Administration of Clinical Application of Medical Technology) within 28 days before the first dose of study treatment and has not yet recovered from which; or any planned curative surgery for renal cell carcinoma during the study.
• •4. History of another malignancy within 5 years before the first dose of study treatment, except for Lung carcinoma in situ, low-risk early-stage prostate cancer, or cured basal-cell carcinoma, squamous-cell carcinoma of the skin, cervical carcinoma in situ, or papillary thyroid carcinoma.
• •5. Clinically significant gastrointestinal abnormalities such as malabsorption syndrome, major gastric or small-bowel resection that may affect drug absorption, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other conditions increasing the risk of perforation; or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days before the first dose of study treatment.
• •6. Systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive agents required within 2 weeks before the first dose or anticipated during study treatment, except for:
• •1. Topical, intranasal, or inhaled corticosteroids.
• •2. Corticosteroids as premedication for infusion-related or hypersensitivity reactions (e.g., premedication for CT imaging).
• •3. Replacement therapy such as levothyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency.
• •4. Low-dose corticosteroids for orthostatic hypotension.
• •7. Clinically significant cardiovascular or cerebrovascular disease documented by any of the following:
• •1. Ischemic stroke (excluding silent lacunar infarction) or severe thromboembolic event within 6 months before the first dose of study treatment.
• •2. Myocardial infarction, unstable angina, congestive heart failure, or clinically significant arrhythmia within 6 months before the first dose of study treatment.
• •3. New York Heart Association (NYHA) class ≥ II heart failure before the first dose of study treatment.
• •4. QTcF interval \>450 ms (men) or \>470 ms (women) before the first dose of study treatment.
• •5. Left-ventricular ejection fraction (LVEF) ≤50 % before the first dose of study treatment.
• •8. Prior organ transplant, except corneal transplant; prior allogeneic stem-cell transplant.
• •9. Hepatitis B surface antigen (HBsAg) positive with HBV DNA \>500 IU/mL or \>2,500 copies/mL, or hepatitis C antibody positive with detectable HCV RNA, or known HIV infection, or active tuberculosis.
• •10. Interstitial lung disease or non-infectious pneumonitis that is currently symptomatic or has previously required systemic corticosteroids, in the opinion of the investigator likely to interfere with toxicity assessment or management.
• •11. Any severe, progressive, or uncontrolled medical condition that, in the investigator's judgment, makes the subject unsuitable for the study, including but not limited to:
• •1. Infection requiring systemic therapy.
• •2. Symptomatic pleural, pericardial, or ascitic fluid requiring or having undergone drainage within 2 weeks before the first dose (minimal asymptomatic effusion, third-spacing due to hypoalbuminaemia, or cases where benefit outweighs risk may be allowed).
• •3. History of coagulopathy (e.g., deep-vein thrombosis) or severe bleeding diathesis; clinically significant bleeding event (e.g., gastrointestinal bleeding) within 1 month before the first dose.
• •4. History of severe psychiatric disorder.
• •5. Any other condition that, in the investigator's opinion, renders study participation riskier than beneficial.
• •12. Prior grade 3-4 immune-related adverse events that, in the investigator's judgment, should be excluded.
• •13. Severe allergic or hypersensitivity disorders, significant drug allergies (including to investigational agents), or known hypersensitivity to any component of the study drug, including severe reactions to monoclonal antibodies.
• •14. Participation in another clinical trial and receipt of an investigational agent within 28 days before the first dose of study treatment.
• •15. Clinically significant organ dysfunction or comorbidity likely to interfere with protocol adherence.
• •16. Live vaccine received within 30 days before the first dose, or planned during the study or within 1 month after the last dose.
• •17. Pregnant or breast-feeding women (women who agree to discontinue breast-feeding before signing informed consent may be enrolled).
• •18. Any other condition or circumstance that, in the investigator's opinion, unsuitable for participation.