A phase III trial recently published in the Journal of Clinical Oncology reviewed nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody that restores T-cell immune activity, for dose-response relationship, safety, and antitumor activity when given to patients with metastatic renal cell carcinoma.
The study randomly assigned patients with clear-cell metastatic renal cell carcinoma who had previously received treatment with agents that target the VEGF pathway to received nivolumab intravenously at a dose of 0.3 mg/kg, 2 mg/kg, or 10 mg/kg every 3 weeks. The study’s primary objective was to measure the dose-response relationship in terms of progression-free survival.
The study’s secondary objectives were safety, overall survival, and objective response rate. The study included 168 patients. Sixty patients were in the 0.3 mg/kg nivolumab cohort, 54 patients were in the 2 mg/kg nivolumab cohort, and 54 patients were in the 10 mg/kg nivolumab cohort. Within all of the cohorts, 118 patients had previously received one or more prior systemic regimen.
The median progression-free survival among the cohorts was 2.7 months, 4 months, and 4.2 months, respectively (P=0.9). Overall response rate among the cohorts was 20%, 22%, and 20%, respectively, and medial 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.
Adverse events were recorded and the most frequent was fatigue—19 patients (11%) experienced adverse events that were categorized as grade 3 or 4.
The researchers concluded that nivolumab showed a manageable safety profile and antitumor activity for all three dose administrations. There was no dose-response relationship identified in relation to progression-free survival. Researchers thus indicate that further phase III testing is warranted.
This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS.