Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma

Clin Pharmacol Ther. 2020 Mar;107(3):588-596. doi: 10.1002/cpt.1645. Epub 2019 Nov 18.


Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10 mg/kg weight-based dose. We report pharmacokinetic (PK)/pharmacodynamic analyses for avelumab comparing weight-based dosing and a flat 800 mg dose, developed using data from 1,827 patients enrolled in 3 clinical trials (NCT01772004, NCT01943461, and NCT02155647). PK metrics were simulated for weight-based and flat-dosing regimens and summarized by quartiles of weight. Derived exposure metrics were used in simulations of exposure-safety (various tumors) and exposure-efficacy (objective responses; Merkel cell or urothelial carcinoma). Flat dosing was predicted to provide similar exposure to weight-based dosing, with slightly lower variability. Exposure-safety and exposure-efficacy simulations suggested similar benefit:risk profiles for the two dosing regimens. These pharmacometric analyses provided the basis for the US Food and Drug Administration approval of a flat dose of avelumab 800 mg every 2 weeks in approved indications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / pharmacokinetics
  • Antineoplastic Agents, Immunological / pharmacology
  • Body Weight
  • Carcinoma, Merkel Cell / drug therapy*
  • Clinical Trials as Topic
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Humans
  • Skin Neoplasms / drug therapy*
  • Urologic Neoplasms / drug therapy*


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • avelumab

Associated data