Which treatment order works best for advanced kidney cancer?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Subjects with histologically confirmed unresectable metastatic renal cell carcinoma (mRCC) will be included in the study. Previous nephrectomy or metastasectomy is allowed, but no prior systemic anticancer therapy targeting RCC is permitted. 2. Classified as low- or intermediate-risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. 3. Male or female subjects aged 18 years or older at the time of signing the informed consent form. 4. Defined as Chinese ethnicity, with both biological parents and all four biological grandparents being of Chinese descent. 5. Patients who progressed or were intolerant to first-line TKI therapy (including sunitinib, pazopanib, cabozantinib, sorafenib, axitinib, lenvatinib, etc.) and subsequently received TKI/IO therapy (including axitinib/ lenvatinib/ cabozantinib combined with toripalimab/ tislelizumab/ pembrolizumab/ sintilimab/ nivolumab, etc.). 6. Patients who progressed or were intolerant to first-line TKI/IO therapy (including axitinib/ lenvatinib/ cabozantinib combined with toripalimab/ tislelizumab/ pembrolizumab/ sintilimab/ nivolumab, etc.) and subsequently received TKI therapy (including sunitinib, pazopanib, cabozantinib, sorafenib, axitinib, lenvatinib, etc.). 7. Karnofsky Performance Status (KPS) ≥ 70% within 10 days prior to the first dose of treatment. 8. Adequate organ function as evidenced by laboratory values: ANC ≥ 1500/μL; platelets ≥ 100,000/μL; hemoglobin ≥ 10.0 g/dL or ≥ 6.2 mmol/L; CrCl ≥ 30 mL/min; AST and ALT ≤ 2.5 × ULN; total bilirubin ≤ 1.5 × ULN; and INR or PT ≤ 1.5 × ULN. Exclusion Criteria: 1. Requiring intermittent oxygen supplementation at rest, or long-term oxygen therapy. 2. Clinically significant cardiovascular disease within 6 months prior to the first dose of study intervention. 3. Severe active, non-healing wound, ulcer, or fracture. 4. Use of colony-stimulating factors (e.g., G-CSF, GM-CSF), recombinant erythropoietin (EPO), or blood transfusion within 28 days prior to the first dose of study intervention. 5. Inability to swallow oral medications or a history of, or current evidence of, gastrointestinal diseases (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function, or other conditions that, in the investigator's opinion, may significantly alter the absorption or metabolism of oral study interventions. 6. Severe hypersensitivity reactions to TKI drugs, IO drugs, and/or any excipients. 7. Diagnosis of immunodeficiency or use of long-term systemic corticosteroids (daily dose exceeding 10 mg prednisone or equivalent) or any form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 8. Diagnosis of another malignancy (excluding RCC treated by nephrectomy and/or metastasectomy) that is currently progressing or required active treatment in the past 3 years. Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding bladder carcinoma in situ) who have undergone potentially curative treatment are eligible. 9. Active autoimmune disease requiring systemic treatment (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment and is allowed. 10. History of or current (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or current pneumonitis/interstitial lung disease. 11. Active infection requiring systemic treatment. 12. Known history of HIV infection, hepatitis B (defined as HBsAg reactive), or active hepatitis C virus (defined as detectable HCV RNA \[qualitative\]). Note: Testing for HIV, HBV, or HCV is not required unless mandated by local health regulations. 13. Any prior or current condition, treatment, laboratory abnormality, or other circumstance that may interfere with the study results, affect the subject's ability to complete the study, or, in the investigator's opinion, make the subject unsuitable for participation or unlikely to benefit from the study. 14. Known psychiatric or substance abuse disorders that would interfere with the subject's ability to comply with study requirements 15. History of prior allogeneic tissue/solid organ transplantation. 16. If the subject is a non-pregnant and non-lactating female, the subject must agree to use highly effective (failure rate \<1% per year) and low-dependency contraceptive methods during treatment.