While the 5-year survival rate for localized renal cell carcinoma (RCC) approaches 80%-95%, patients with high-risk non-metastatic disease face a substantial 30%-40% risk of recurrence/metastasis within 5 years. Emerging evidence demonstrates that combining anti-angiogenic agents with immune checkpoint inhibitors significantly extends progression-free survival (PFS) in first-line advanced/metastatic RCC settings. To address the unmet need for adjuvant strategies in intermediate/high-risk localized RCC, we propose a synergistic approach leveraging targeted therapy and immunotherapy. This dual-modality regimen may delay resistance mechanisms while enhancing disease-free survival (DFS) and overall survival (OS). Vorolanib, a next-generation vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitor (TKI), exhibits unique pharmacodynamic properties that warrant investigation in adjuvant paradigms. This study evaluates two experimental arms: (1) Vorolanib combined with toripalimab, a PD-1 inhibitor. (2) Vorolanib monotherapy. This study aims to evaluate the efficacy and safety of vorolanib combined with toripalimab or vorolanib monotherapy in postoperative adjuvant therapy for intermediate/high-risk non-metastatic locally advanced renal cell carcinoma (RCC), while also investigating the correlation between postoperative minimal residual disease (MRD)-positive status and recurrence risk.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
200mg PO QD
Vorolanib: 100mg PO QD Toripalimab: 240mg IV infusion Q3W
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
2-y DFS
The proportion of patients who did not experience local recurrence/transfer or died for any reason within 2 years among all patients, per RECIST or irRECIST
Time frame: From enrollment to the recurrence or metastasis or death(based on the first occurrence) at 2 years
DFS
The period from the date of enrollment until local recurrence or distant metastasis occurs, or until death due to any cause, shall be measured from the earlier of the two events, per RECIST 1.1 and irRECIST
Time frame: From date of enrollment until the date of local recurrence or distant metastasis occurs, or date of death from any cause ,whichever came first,assessed up to 100 months
OS
The period from the date of enrollment until the date of death due to any cause
Time frame: From date of enrollment to death due to any cause,assessed up to 120 months
Safety and tolerability
The proportion of patients experiencing adverse events among the total patients, per CTCEA v5.0
Time frame: 1 year
The correlation between MRD positivity and recurrence
The correlation between postoperative MRD (Minimal Residual Disease) positive status and postoperative recurrence
Time frame: up to 2 years
Correlation between molecular characteristics and therapeutic efficacy
Calculate the MRD positive rate of the patients.All of the patients were divided into negative group and positive group based on the MRD status.Evaluate the RFS of the two groups separately, and the evaluation index was the hazard ratio(HR)value.
Time frame: up to 2 years
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