Journal List > Transl Clin Pharmacol > v.24(1) > 1082644

Kim and Jung: Clinical pharmacologic aspects of immune checkpoint inhibitors in cancer therapy

Abstract

During the past two years, three immune checkpoint inhibitors, ipilimumab, nivolumab and pem-brolizumab, have been approved and revolutionized cancer immunotherapy. Translational and clinical pharmacology of these agents have contributed in identifying patients who will receive benefit, dose effect relationship and surrogate endpoints of clinical benefit. In addition, population pharmacokinetics/pharmacodynamics have facilitated scientific clinical development, which has led to accelerated approval of these agents. This paradigm may show how early phase studies may allow identification of subgroup of patients who can benefit and subsequent approval of drugs based on smaller patient population. This may speed the access of effective treatment for patients with life-threatening diseases.

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Table 1.
Pharmacokinetic characteristics of approved immune checkpoint inhibitors
  Immunoglobulin subtype Systemic Clearance Volume of distribution at steady state Terminal half-life
Ipilimumab IgG1 15.3 mL/h (38.5%) 7.21 L (10.5%) 14.7 days (30.1%)
Nivolumab IgG4 9.5 mL/h (49.7%) 8.0 L (30.4%) 26.7 days (101%)
Pembrolizumab IgG4 8.3 mL/h (28%) 7.7 L (14%) 26 days (24%)

Mean (percent coefficient of variation) based on FDA package insert values.

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