An exploratory study of the biologic effects of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) treatment in patients (pts) with advanced (unresectable or metastatic) melanoma (MEL).

Abstract

TPS3114 Background: Programmed death-1 (PD-1) is an immune checkpoint receptor expressed by T cells that negatively regulates T-cell activity and may promote tumor immune evasion by binding to its ligands (PD-L1/L2) on tumor cells and/or antigen-presenting cells. Nivolumab is a fully human IgG4 PD-1 receptor blocking monoclonal antibody that has shown antitumor activity in phase I trials in pts with solid tumors, including advanced MEL. Objective responses were observed in pts whose diseases were refractory to multiple prior therapies. We describe an ongoing exploratory, open-label, multicenter translational study designed to further investigate the immunoregulatory activity and mechanisms of action of nivolumab in advanced MEL, including ipilimumab (anti-CTLA-4) naïve and refractory pts. Methods: This study is enrolling advanced MEL pts who are either ipilimumab naive (n=40) or refractory (n=40). Eligible pts must not have received >3 prior therapies for metastatic disease and must consent to pre-and on-treatment biopsy (after 2 doses of nivolumab [Day 28]) of an accessible tumor. Nivolumab will be administered IV every 2 weeks (wks) at a dose of 3mg/kg and may continue for up to 13 cycles (104 wks) until clinically significant progression or treatment discontinuation criteria are met. Tumor responses will be assessed every 8 wks using RECIST 1.1 criteria. The primary objective is to investigate the pharmacodynamic (immunoregulatory) activity of nivolumab in the peripheral blood (PB), tumor, and tumor microenvironment. Secondary objectives include evaluation of safety and tolerability, preliminary antitumor activity, and immunogenicity of nivolumab, as well as the association between tumor PD-L1 expression and clinical efficacy. Exploratory objectives include characterization of pharmacokinetics (PK) and evaluation of the potential association between selected PB and/or tumor biomarkers and PK, clinical safety, and efficacy (eg, progression-free and overall survival). Clinical trial information: NCT01621490.