Nivolumab, a checkpoint-inhibitor that blocks the PD-1 receptor and enhances anti-tumor activity in patients with renal cell carcinoma (RCC), has completed a large phase I trial to demonstrate its efficacy and safety. The PD-1 receptor works to slow down or stop immune response including anti-tumor immune response. By inhibiting PD-1 receptor, nivolumab could switch off the brake of immune response and allow anti-tumor activity.
In the phase I study led by Brian I. Rini, MD, patients with various types of tumor (including 34 patients with advanced RCC) were enrolled. The overall response rate (ORR) was 29% for patients with RCC, demonstrating a clear anti-tumor activity with nivolumab as a single-agent. This percentage is much higher than the one with previous immunothrapies (cytokine therapy with interleukin-2), which demonstrated 5% to 10% of ORR.
Nivolumab is being developed for kidney cancer treatment in combination with ipilimumab, an inhibitor of a receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). CTLA-4 receptor also plays a role to slow down or stop immune system.
A phase III trial is underway to compare nivolumab to an anti-cancer drug everolimus for the patients with advancerd RCC. The endpoints in this study are overall survival (OS), progression-free survival and overall response rate (ORR). OS will be assessed in PDf ligand 1 (PD-L1) positive and negative subgroups to see whether PD-L1 could be a biomarker of response.
Panelists related to this study included Robert A. Figlin, MD, Cedars-Sinai; Daniel J. George, MD, Duke; Thomas E. Hutson, DO, PharmD, Texas Oncology; Eric Jonasch, MD, MD Anderson; Brian I. Rini, MD, Cleveland Clinic
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