DDMODEL00000284: Bajaj_2017_PK_Nivolumab

  public model
Short description:
Nivolumab PK is linear with a time varying clearance.
Original code
  • Model-Based population pharmacokinetics analysis of Nivolumab in patients with solid tumors
  • Y Feng, G Bajaj, X Wang, S Agrawal, M Gupta, A Roy
  • CPT: Pharmacometrics & Systems Pharmacology, 2/2018, Volume 1, Issue 6, pages: 58-66
  • Bristol-Myers Squibb
  • Nivolumab is a fully human monoclonal antibody that inhibits programmed death-1 activation. The clinical pharmacology profile of nivolumab was analyzed by a population pharmacokinetics model that assessed covariate effects on nivolumab concentrations in 1,895 patients who received 0.3–10.0 mg/kg nivolumab in 11 clinical trials. Nivolumab pharmacokinetics is linear with a time-varying clearance. A full covariate model was developed to assess covariate effects on pharmacokinetic parameters. Nivolumab clearance and volume of distribution increase with body weight. The final model included the effects of baseline performance status (PS), baseline body weight, and baseline estimated glomerular filtration rate (eGFR), sex, and race on clearance, and effects of baseline body weight and sex on volume of distribution in the central compartment. Sex, PS, baseline eGFR, age, race, baseline lactate dehydrogenase, mild hepatic impairment, tumor type, tumor burden, and programmed death ligand-1 expression had a significant but not clinically relevant (<20%) effect on nivolumab clearance.
Andre Jackson
Context of model development: Mechanistic Understanding;
Discrepancy between implemented model and original publication: None;
Long technical model description: Nivolumab pharmacokinetics is linear with a time-varying clearance. A full covariate model was developed to assess covariate effects on pharmacokinetic parameters. Nivolumab clearance and volume of distribution increase with body weight. The final model included the effects of baseline performance status (PS), baseline body weight, and baseline estimated glomerular filtration rate (eGFR), sex, and race on clearance, and effects of baseline body weight and sex on volume of distribution in the central compartment. Sex, PS, baseline eGFR, age, race, baseline lactate dehydrogenase, mild hepatic impairment, tumor type, tumor burden, and programmed death ligand-1 expression had a significant but not clinically relevant (<20%) effect on nivolumab clearance.;
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: This analysis assessed the clinical relevance of demographic and pathophysiological covariates affecting PK of nivolumab. The model also explored the PK of nivolumab across tumor types and was used to determine individual exposures in patients to support exposureâ?? response analyses for target populations. This analysis serves as an example for characterizing time-varying clearance for monoclonal antibodies.;
Modelling task in scope: estimation;
Nature of research: Early clinical development (Phases I and II);
Therapeutic/disease area: Immunology;
Annotations are correct.
This model is not certified.
  • Model owner: Andre Jackson
  • Submitted: Apr 4, 2018 9:26:21 AM
  • Last Modified: Apr 4, 2018 9:26:21 AM
Revisions
  • Version: 11 public model Download this version
    • Submitted on: Apr 4, 2018 9:26:21 AM
    • Submitted by: Andre Jackson
    • With comment: Updated model annotations.
 
Help