TPS4630 Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases worldwide and 60-85% in China. High risk ccRCC includes tumors larger than 7 cm (T2 stage) or those at advanced stages (≥T3 or N1). Surgical resection is standard, but 30% may have recurrence, with a 2-year disease-free survival rate of 68%. Neoadjuvant therapy with axitinib and toripalimab may enhance antitumor immunity and improve prognosis for high risk patients. Methods: This is an open-label, multicenter, phase III randomized controlled study to assess whether neoadjuvant axitinib plus toripalimab improves disease-free survival (DFS) compared with surgery alone in patients with ccRCC at high risk of recurrence. The study is designed to enroll 298 patients with high risk ccRCC (T2G4 or T3-4 or N1) scheduled for nephrectomy. Patients must provide an adequate tumor tissue sample at screening for molecular and immune profiling. Patients will be randomly assigned to the control group or the neoadjuvant group at a 1:1 ratio. Both groups will undergo nephrectomy, while the neoadjuvant group will additionally receive preoperative treatment with axitinib plus toripalimab. Axitinib will be given for 3 months, 5 mg twice daily, orally. Toripalimab will be administered at 240 mg intravenously every 3 weeks for 4 cycles (one cycle every 3 weeks). Blood samples are collected before and after neoadjuvant treatment for exploratory molecular analysis. CT or MRI assessments will be conducted after 2 cycles of medication and before surgery. Radical nephrectomy (or partial nephrectomy, if applicable) will be performed within 1-28 days after completion of neoadjuvant therapy. For both groups, if postoperative pathology meets high recurrence risk criteria per Keynote-564—specifically, T2G4, T2 with sarcomatoid differentiation, T3, T4, any T stage with lymph node metastasis, or M1 with no evidence of disease—1 year of adjuvant toripalimab is recommended according to NCCN and EAU guidelines. Eligible patients must be diagnosed as ccRCC or RCC with a predominant clear cell component through histopathological examination. Clinical staging via CT or MRI must indicate T2, while biopsy pathology should show either nuclear grade 4 or sarcomatoid differentiation, or a classification of T3-4 or N1. Additional inclusion criteria include: signed informed consent, age ≥18 and < 80 years old, adequate organ function, ECOG of 0 or 1 point. The primary endpoint is 2-year DFS, defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints include cancer-specific survival, overall survival, objective response rate, major pathological response, and safety profile. Enrollment began in April 2023, and 112 of the planned 298 patients have been enrolled. Clinical trial information: NCT05738694 .
Zhang et al. (Thu,) studied this question.