Vorolanib Monotherapy or in Combination With Toripalimab as Adjuvant Therapy for Patients With Intermediate-high Risk of Recurrence in Renal Cell Carcinoma

Prior treatment

• Prior exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies, or other agents specifically targeting T-cell co-stimulation checkpoints, or small molecule anti-angiogenic drugs.
• Subjects who underwent major surgery or chemotherapy within 4 weeks prior to the first dose administration, or those with postoperative duration \>12 weeks who received major surgery/chemotherapy within 4 weeks before first dosing.
• Severe infections requiring IV antibiotics/antifungals/antivirals within 4 weeks prior to first dose, or unexplained fever \>38.5°C during screening.
• Systemic corticosteroids or immunosuppressants within 14 days before first study drug administration.
• Concurrent use of experimental agents or standard antineoplastic therapies.

Other illness

• Subjects with hypersensitivity to study drugs.
• Active hemorrhage, ulceration, intestinal perforation, bowel obstruction, or uncontrolled hypertension (defined as BP \>140/90 mmHg or unstable during screening).
• Uncontrolled adrenal insufficiency.
• Active autoimmune diseases (including but not limited to autoimmune hepatitis, interstitial lung disease, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism) or history of autoimmune diseases. Exceptions: Vitiligo or childhood asthma fully resolved without intervention in adulthood.
• History of other malignancies within 5 years.
• Documented active tuberculosis (Mycobacterium tuberculosis).
• Active infections.
• High bleeding risk.
• Comorbidities (e.g., cardiopulmonary insufficiency) precluding radical nephrectomy/partial nephrectomy under general anesthesia.
• Other conditions affecting trial conduct or interpretation (e.g., severe psychiatric disorders).

Lab values

• Congenital/acquired immunodeficiency (e.g., HIV infection) or active hepatitis:
  • HBV: HBsAg+ with HBV DNA ≥2000 IU/mL (≥10⁴ copies/mL) HCV: Anti-HCV+ with viral load \>ULN

Other

• Patients with advanced/metastatic renal cell carcinoma (RCC) or non-clear cell renal cell carcinoma (nccRCC).
• Symptomatic visceral metastases with imminent life-threatening complications (e.g., uncontrolled exudation \[pleural/pericardial/abdominal\], lymphangitic carcinomatosis, or \>30% liver involvement).
• Pregnant/lactating women.

• Has histologically confirmed diagnosis of localized and locally advanced stage renal cell carcinoma (RCC), with moderate to high recurrence risk
• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
  • Intermediate-high risk RCC: pT1b-T2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0;
  • High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0 M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous)
• Have adequate tissue for PD-L1 testing 0Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
• Expected survival ≥ 12 months;
• Participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment
• Has adequate organ function
• Be able to understand and willing to sign the informed consent form