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

Hongshan Li1, Jingyu Yu1, Chao Liu1

  • 1Food and Drug Administration, Silver Spring, MD, USA.

Journal of Pharmacokinetics and Pharmacodynamics
|June 3, 2017
PubMed

Insights

Pembrolizumab

Area of Science:

  • Immunology
  • Pharmacology
  • Oncology

Background:

  • Pembrolizumab is an immunotherapy drug targeting the PD-1 receptor.
  • Initially approved for melanoma, its use expanded to lung, lymphoma, head/neck, and urothelial cancers.
  • Pharmacokinetic studies are crucial for optimizing cancer therapy.

Purpose of the Study:

  • To characterize the time-dependent changes in pembrolizumab's clearance (CL).
  • To investigate the relationship between pharmacokinetic parameters and treatment response.

Main Methods:

  • Analysis of pembrolizumab pharmacokinetic data over time.
  • Modeling of time-varying clearance using a sigmoidal function.
  • Correlation of pharmacokinetic parameters with objective response in solid tumors.

Main Results:

  • Pembrolizumab clearance (CL) decreases over the treatment period.
  • This time-dependent CL is accurately described by a sigmoidal model.
  • The magnitude of Imax, a parameter reflecting maximum change in CL, correlates with treatment response.

Conclusions:

  • Pembrolizumab exhibits time-varying clearance, a significant pharmacokinetic characteristic.
  • Understanding this time-dependency is key for personalized dosing strategies.
  • Pharmacokinetic variability, particularly Imax, is linked to clinical efficacy in cancer patients.
Keywords:
Best overall responseImmunotherapyMonoclonal antibodyOncologyPD-1PembrolizumabTime dependent pharmacokineticsTime varying clearance

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