Pharmacokinetics of MEDI4736, a fully human anti-PDL1 monoclonal antibody, in patients with advanced solid tumors.

2602 Background: MEDI4736 is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against human programmed death ligand 1 (PD-L1). MEDI4736 blocks inhibitory interaction of PD-L1 with the PD-1 (CD279) and B7-1 (CD80) molecules, and enhances T-cell activation. The primary objectives of this analysis were to assess the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of MEDI4736 in patients with advanced solid tumors. Methods: Data were collected from a Phase 1 study (NCT01693562) designed to evaluate safety, tolerability and PK following 0.1, 0.3, 1.0, 3.0, and 10 mg/kg every 2 weeks (Q2W) and 15 mg/kg every 3 weeks (Q3W) intravenous (IV) doses of MEDI4736. A total of 32 patients provided evaluable data. PK, ADA and soluble PD-L1 (sPD-L1) as PD were measured using validated electrochemiluminescence assays in human serum. Data analysis was performed using Phoenix Winnonlin and NONMEM software. Results: Area under the curve (AUC) increased more than dose-proportionally over th...