Nivolumab is a fully human monoclonal antibody that is directed toward the immune checkpoint receptor programmed death-1 (PD-1). A phase 1 dose-escalation/cohort expansion study demonstrated encouraging antitumor activity and tolerability in 107 ipilimumab-naïve previously treated patients with advanced melanoma; patients received nivolumab 0.1, 0.3, 1, 3, or 10 mg/kg intravenously every 2 weeks for up to 96 weeks. McDermott and colleagues reported the long-term clinical activity, response duration off-therapy, and correlative studies with tumor programmed death-ligand 1 (PD-L1) expression of this trial (McDermott D, et al. ESMO 2014: Abstract 1088PD). Objective responses by RECIST criteria were achieved by 34 of 107 (32%) patients; the median duration of response was 99.4 weeks. These responses are ongoing in 19 of 34 (56%) patients. The objective response rate in the 3-mg/kg dose cohort was 41% (7/17), and was chosen as the dose for future phase 3 clinical trials. Responses were rapid, with 44% of responders achieving responses at first tumor assessment (6 weeks). Of the 21 responding patients who discontinued nivolumab for reasons other than disease progression, 11 (52%) maintained responses for ?24 weeks off the drug. Updated overall survival (OS) analysis showed that nivolumab therapy was associated with OS rates of 63%, 48%, and 41%, at year 1, year 2, and year 3, respectively. Median OS was 17.3 months across doses, and the median progression-free survival (PFS) was 3.7 months across dose cohorts. Based on PD-L1 expression status using a 5% tumor-cell surface-staining cut-off in a subset of 41 patients with available tumor samples, median OS was not reached for the 18 patients (44%) who had PD-L1–positive tumors and 12.5 months for the 23 patients (52%) who had PD-L1–negative tumors, with a median PFS of 9.1 and 1.9 months, respectively. No new treatment-related toxicities emerged in this study; common adverse events with nivolumab therapy included skin, gastrointestinal, hepatic, and endocrine toxicities as previously described. McDermott and colleagues concluded that nivolumab therapy in patients with advanced melanoma demonstrated promising 2-year and 3-year OS rates, durable responses, and an acceptable safety profile, with greater benefit seen in patients with PD-L1–positive disease.
