Nivolumab is a fully human IgG4 monoclonal antibody that blocks the binding of the programmed cell death receptor-1 protein (PD-1) to its endogenous ligands PD-L1 and PD-L2. The inhibition of these interactions has demonstrated to enhance T-cell response and thus cell-mediated immune responses against tumour cells.
In Europe, nivolumab is under accelerated assessment for the first- and second-line treatment of advanced (unresectable or metastatic) melanoma. In the US, the drug was approved under accelerated approval by the FDA in December 2014 for the treatment of patients with unresectable or metastatic melanoma with disease progression following ipilimumab therapy and, if BRAF V600 mutation-positive, a BRAF inhibitor.
In an interim analysis of data from CheckMate 066, a phase III trial which had compared nivolumab to dacarbazine in patients without BRAF mutations, nivolumab showed a survival benefit compared to dacarbazine. Median PFS was extended by 2.9 months with nivolumab in comparison to dacarbazine, and the OS rate after one year was 73% vs. 42%. At the interim analysis, median OS and the duration of response with nivolumab had not been reached yet, as response was durable over the (short) follow-up period.
Adverse events (AEs) were very common in both groups, but treatment-related AEs of grade 3 or 4 were more frequent in the dacarbazine group (18%) than in patients treated with nivolumab (12%). Also more patients with dacarbazine discontinued therapy due to AEs (dacarbazine 12% vs. nivolumab 7%).
Even though cost estimates are not yet available, costs comparable to those of ipilimumab can be expected. Since its administration in combination with other agents can be expected in patients with melanoma, and due to nivolumab being under investigation also for common types of cancer (such as non-small cell lung cancer), the initial pricing is of utmost importance.