Pharmacokinetics and pharmacodynamics of MEDI4736, a fully human anti-programmed death ligand 1 (PD-L1) monoclonal antibody, in patients with advanced solid tumors.

2015 
e14009 Background: MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD-80 with high affinity and selectivity. 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 doses of MEDI4736. A total of 377 patients provided evaluable PK and soluble PD-L1 (sPD-L1) data. ADA data were available from 386 subjects. PK, sPD-L1, and ADA were measured using validated electrochemiluminescence assays in human serum. Data analysis was performed using Phoenix WinNonlin and GraphPad Prism software. Results: Area under the curve (AUC) increased more than dose proportionally over the dose range of 0.1 to 10 mg/kg Q2W or 15 mg/kg Q3W and approached linearity at ≥ 3 mg/kg Q...
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