Nivolumab ( Opdivo ) is a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody that restores T-cell immune activity.
This phase II trial assessed the antitumor activity, dose-response relationship, and safety of Nivolumab in patients with metastatic renal cell carcinoma ( mRCC ).
Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned ( blinded ratio of 1:1:1 ) to Nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks.
The primary objective was to evaluate the dose-response relationship as measured by progression-free survival ( PFS ); secondary end points included objective response rate ( ORR ), overall survival ( OS ), and safety.
A total of 168 patients were randomly assigned to the Nivolumab 0.3- ( n = 60 ), 2- ( n = 54 ), and 10-mg/kg ( n = 54 ) cohorts. One hundred eighteen patients ( 70% ) had received more than one prior systemic regimen.
Median progression-free survival was 2.7, 4.0, and 4.2 months, respectively ( P = 0.9 ).
Respective ORRs were 20%, 22%, and 20%.
Median overall survival was 18.2 months ( 80% CI, 16.2 to 24.0 months ), 25.5 months ( 80% CI, 19.8 to 28.8 months ), and 24.7 months ( 80% CI, 15.3 to 26.0 months ), respectively.
The most common treatment-related adverse event was fatigue ( 24%, 22%, and 35%, respectively ). Nineteen patients ( 11% ) experienced grade 3 to 4 treatment-related adverse effects.
In conclusion, Nivolumab has demonstrated antitumor activity with a manageable safety profile across the three doses studied in metastatic renal cell carcinoma.
No dose-response relationship was detected as measured by progression-free survival. These efficacy and safety results in metastatic renal cell carcinoma support study in the phase III setting. ( Xagena )
Motzer RJ et al, J Clin Oncol 2014; Epub ahead of print