Time dependent pharmacokinetics of pembrolizumab in patients with solid tumor and its correlation with best overall response

AbstractPembrolizumab is a monoclonal antibody that targets the programmed death-1 receptor to induce immune-mediated clearance (CL) of tumor cells. Originally approved by the US Food and Drug Administration in 2014 for treating patients with unresectable or metastatic melanoma, pembrolizumab is now also used to treat patients with non-small-cell lung cancer, classical Hodgkin lymphoma, head and neck cancer, and urothelial cancer. This paper describes the recently identified feature of pembrolizumab pharmacokinetics, the time-dependent or time-varying CL. Overall results indicate that CL decreases over the treatment period of a typical patient in a pattern well described by a sigmoidal function of time with three parameters: the maximum proportion change in CL from baseline (approximately Imax or exactly eImax − 1), the time to reach Imax/2 (TI50), and a Hill coefficient. Best overall response per response evaluation criteria in solid tumor category was found to be associated with the magnitude of Imax.
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research