Evaluation of the pharmacokinetics and metabolism of pembrolizumab in the treatment of melanoma

ABSTRACT

Introduction: Advanced melanoma is a devastating disease that has propelled research in therapeutics beyond chemotherapy and radiotherapy. Being highly immunogenic, melanoma is a model tumor for immunotherapy and has highlighted the therapeutic potential of the immune checkpoint inhibitors.

Areas covered: This review discusses the pharmacologic properties, clinical efficacy, and safety profile of pembrolizumab, an IgG4-kappa humanized monoclonal antibody against the programmed cell death protein 1 (PD-1) receptor, for the treatment of unresectable or metastatic melanoma.

Expert opinion: Pembrolizumab was the first PD-1 inhibitor to be approved by the U.S. Food and Drug Administration (FDA). Remarkably, this accelerated approval for the treatment of advanced, heavily pretreated melanoma was based on response rates alone from a phase I trial. As anticipated, pembrolizumab confirmed a survival advantage in phase II and III trials and has led the way for the study of other drugs that share its mechanism of action. Defining disease and patient characteristics associated with a response remains amongst the most pressing priorities.

KEYWORDS:

• Immune checkpoint
• melanoma
• pembrolizumab
• PD-1

Box 1. Drug summary

Table

Declaration of interest

KS Tewari has served as a consultant for Genetech/Roche and that his institution has been awarded a research grant from Genentech for contracted research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was supported by the Ruth L. Kirschstein NRSA Institutional Training Research Grant, 2T32 CA06039611 awarded to the Division of Gynecologic Oncology at the University of California, Irvine.