Abstract
TPS4592 Background: Standard approved treatments for pts with mRCC include interleukin-2 as well as therapies that target the vascular endothelial growth factor (eg, sunitinib, pazopanib) or mammalian target of rapamycin (eg, temsirolimus, everolimus) pathways. However, most pts may develop resistance, and overall survival (OS) improvement has only been shown in one phase 3 trial in poor-risk pts. Everolimus demonstrated a 3-month improvement in median progression-free survival (PFS) vs placebo, with no OS improvement (Motzer RJ, et al. Lancet. 2008;372:449-56). A phase 1 study of the fully human programmed death-1 (PD-1) receptor blocking monoclonal antibody nivolumab showed encouraging antitumor activity with previously treated mRCC (objective response rate [ORR], 29% (10/34); stable disease at ≥24 weeks [wks], 27% [9/34]). PD-1 is an immune checkpoint receptor that negatively regulates T-cell activation and PD-1 overexpression by tumor infiltrating lymphocytes has been associated with poor prognosis in multiple tumor types. Therefore, an ongoing, randomized, open-label, global phase 3 trial was developed to evaluate the clinical benefit of nivolumab in mRCC pts previously treated with anti-angiogenic therapy. Methods: Approximately 822 pts with advanced or metastatic clear-cell mRCC who have received ≤2 prior anti-angiogenic therapies and ≤3 total prior systemic regimens will be randomized 1:1 to receive nivolumab 3 mg/kg IV every 2 wks (Arm A) or everolimus 10 mg PO daily (Arm B). Pts will be stratified by region, MSKCC risk group, and number of prior anti-angiogenic therapy regimens. Tumor response will be assessed using RECIST 1.1 every 8 wks following randomization for the first year and then every 12 wks until disease progression or treatment discontinuation, whichever occurs later. The primary endpoint is OS. Secondary endpoints include PFS, ORR, OR duration, adverse events, OS in PD ligand 1 (PD-L1) positive or negative subgroups, and patient-reported outcomes. The trial is open and enrolling pts. Clinical trial information: NCT01668784.
Published Version
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