Assistant Professor University of Alabama at Birmingham, AL, United States
Background: Molecular Residual Disease (MRD) assays are high sensitivity and specificity circulating tumor DNA assays that are designed to identify patients at high risk of recurrence after surgical intervention. Emerging data suggests that these assays can be used as a prognostic marker in various tumor types including in renal cell carcinoma (RCC). Pembrolizumab is currently the only approved adjuvant immunotherapy for high risk resected RCC patients. Several adjuvant immunotherapy trials have not proven any clinical benefit. We designed a study to incorporate a MRD-guided approach to the assignment of adjuvant immunotherapy to obtain early estimates of clinical outcomes as a initial step to design larger biomarker integral clinical trials in adjuvant RCC.
Methods: Key inclusion criteria include age ≥18 years, histologically confirmed clear cell RCC of intermediate-high risk (pT2, grade 4 or sarcomatoid, N0 M0; or pT3, any grade, N0 M0), high risk (pT4, any grade, N0 M0; or pT any stage, any grade, N+ M0), ; no prior systemic therapy for advanced RCC; positive surgical margins are allowed; Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2; and tumor sample available for development of MRD probe. M1 NED patients are excluded from this study. Patients will be assigned to receive pembrolizumab 400 mg every 6 weeks by intravenous infusion only if found to be MRD positive within 3 months of surgical resection. Treatment will continue until disease recurrence, treatment discontinuation, or completion. Imaging will be performed based on NCCN guidelines. The primary end point is disease-free survival (DFS) per investigator assessment at 1 year . The secondary end point is overall survival (OS) at 1 year . An anticipated 100 patients will be accrued across an estimated 5-6 centers. [
Funding: National Comprehensive Cancer Center Network]
