Personalized combo therapy aims to overcome drug resistance in 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. Voluntarily agree to participate in the study and be willing and able to sign the informed consent form. 2. Histologically confirmed clear cell renal cell carcinoma. 3. Advanced renal cell carcinoma not suitable for curative surgery or radiotherapy, or metastatic renal cell carcinoma, AJCC stage IV. 4. No prior systemic therapy for renal cell carcinoma, except for prior adjuvant or neoadjuvant therapy for completely resectable renal cell carcinoma, provided that the therapy did not include agents targeting VEGF or VEGFR and recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy. 5. At least one measurable lesion according to RECIST version 1.1. 6. Karnofsky Performance Status score ≥70. 7. Estimated life expectancy of more than 3 months. 8. Aged 18 to 75 years. 9. Adequate major organ function and hematologic function, including: * Absolute neutrophil count ≥1500 cells/μL without granulocyte colony-stimulating factor support within 2 weeks before Cycle 1 Day 1. * Platelet count ≥80 × 10\^9/L. * White blood cell count ≥2500/μL and ≤15000/μL without G-CSF support. * Lymphocyte count ≥500/μL. * Hemoglobin ≥9.0 g/dL, without erythropoietin dependence and without packed red blood cell transfusion within the previous 2 weeks. * ALT, AST, and alkaline phosphatase ≤3 × upper limit of normal; ≤5 × upper limit of normal is allowed for liver metastases. For participants with bone metastases, alkaline phosphatase ≤5 × upper limit of normal is allowed. * Total bilirubin ≤1.5 × upper limit of normal. Participants with known Gilbert syndrome may be enrolled if total bilirubin is ≤3 × upper limit of normal. * Serum albumin ≥2.8 g/dL. * Serum creatinine ≤2.0 × upper limit of normal or calculated creatinine clearance ≥30 mL/min. * Urine protein-to-creatinine ratio ≤1 mg/mg, equivalent to ≤113.2 mg/mmol. 10. Female participants who are not postmenopausal or surgically sterile must agree to use two adequate contraceptive methods, including at least one method with an annual failure rate of less than 1%. 11. Sexually active participants of reproductive potential and their partners must agree to use medically accepted contraceptive methods during the study and for 5 months after the last dose for female participants and 7 months after the last dose for male participants. 12. Female participants of childbearing potential must not be pregnant at screen Exclusion Criteria: 1. Prior systemic therapy for renal cell carcinoma, unless the investigator can provide evidence that the participant was assigned to a placebo group. 2. Known central nervous system metastases. 3. Active malignancy within the past 24 months, except for renal cell carcinoma, definitively treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder. Participants with a history of localized low-risk prostate cancer may be eligible if they received curative treatment and have had no prostate-specific antigen recurrence within the past 5 years. 4. Radiotherapy within 21 days before initiation of study treatment, except palliative radiotherapy for bone lesions completed at least 2 weeks before study treatment. 5. Participation in another clinical study or receipt of an investigational drug within 4 weeks before initiation of study treatment. 6. Receipt of a live vaccine within 30 days before planned initiation of study treatment. 7. Proteinuria \>1+ on urine dipstick. Participants with urine protein ≥1 g/24 hours on 24-hour urine collection are not eligible. 8. Fasting total cholesterol \>300 mg/dL, equivalent to 7.75 mmol/L, and/or fasting triglycerides \>2.5 × upper limit of normal. 9. Uncontrolled diabetes mellitus, defined as fasting blood glucose \>1.5 × upper limit of normal. Participants may be enrolled after glucose-lowering treatment if adequately controlled. 10. Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued bisphosphonate or denosumab therapy. 11. QTc interval \>480 ms. 12. Inadequate recovery from toxicity or complications caused by major surgery before treatment initiation. 13. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that may affect absorption of study drugs. 14. Clinically significant hematuria, hematemesis, or hemoptysis of more than 0.5 teaspoon, approximately 2.5 mL, of red blood within 12 weeks before the first dose, or any other significant bleeding history. 15. Significant cardiovascular impairment within 12 months before the first dose, including New York Heart Association class II or higher congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident, or hemodynamically unstable arrhythmia. Participants with left ventricular ejection fraction below the institutional lower limit of normal are also excluded. 16. Active infection requiring systemic treatment. 17. Positive human immunodeficiency virus test. 18. Active hepatitis B or hepatitis C infection. 19. Known history or evidence of interstitial lung disease. 20. History of non-infectious pneumonitis requiring steroids or current pneumonitis. 21. Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or other immunosuppressive therapy within 7 days before the first dose. Physiologic corticosteroid doses up to prednisone 10 mg/day or equivalent are permitted. 22. Active autoimmune disease requiring systemic treatment within the past 2 years, except psoriasis. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy, is not considered systemic treatment. 23. Breastfeeding or pregnancy at screening or baseline. 24. Female participants of childbearing potential who do not agree to use highly effective contraception during the study and for 120 days after study termination. 25. Male participants who have not undergone successful vasectomy and do not agree to use condoms with spermicide from the first dose until 120 days after the last dose, unless abstinent. 26. Known intolerance to any study drug or any excipient. 27. Prior allogeneic tissue or solid organ transplantation. 28. Participants requiring analgesics must be on a stable analgesic regimen at study entry. 29. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage once monthly or more frequently. 30. Uncontrolled hypertension, defined as persistent systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg. 31. Inability to swallow tablets or capsules.