Population Pharmacokinetics of Durvalumab in Cancer Patients and Association With Longitudinal Biomarkers of Disease Status.

Journal Article (Journal Article)

The objectives of this analysis were to develop a population pharmacokinetics (PK) model of durvalumab, an anti-PD-L1 antibody, and quantify the impact of baseline and time-varying patient/disease characteristics on PK. Pooled data from two studies (1,409 patients providing 7,407 PK samples) were analyzed with nonlinear mixed effects modeling. Durvalumab PK was best described by a two-compartment model with both linear and nonlinear clearances. Three candidate models were evaluated: a time-invariant clearance (CL) model, an empirical time-varying CL model, and a semimechanistic time-varying CL model incorporating longitudinal covariates related to disease status (tumor shrinkage and albumin). The data supported a slight decrease in durvalumab clearance with time and suggested that it may be associated with a decrease in nonspecific protein catabolic rate among cancer patients who benefit from therapy. No covariates were clinically relevant, indicating no need for dose adjustment. Simulations indicated similar overall PK exposures following weight-based and flat-dosing regimens.

Full Text

Duke Authors

Cited Authors

  • Baverel, PG; Dubois, VFS; Jin, CY; Zheng, Y; Song, X; Jin, X; Mukhopadhyay, P; Gupta, A; Dennis, PA; Ben, Y; Vicini, P; Roskos, L; Narwal, R

Published Date

  • April 2018

Published In

Volume / Issue

  • 103 / 4

Start / End Page

  • 631 - 642

PubMed ID

  • 29243223

Pubmed Central ID

  • PMC5887840

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1002/cpt.982


  • eng

Conference Location

  • United States