Prediction of Human Pharmacokinetics and Clinical Effective Dose of SI-B001, an EGFR/HER3 Bi-specific Monoclonal Antibody

J Pharm Sci. 2020 Oct;109(10):3172-3180. doi: 10.1016/j.xphs.2020.06.015. Epub 2020 Jun 18.


SI-B001 is a new EGFR/HER3 bi-specific antibody showing encouraging anti-tumor efficacy in the preclinical studies and was ready for further clinical research. To help with the dose design, human pharmacokinetics (PK) and clinical effective doses of SI-B001 were predicted by PK and PK/PD modeling and simulation. A Michaels-Menten (M-M) PK model was first used to describe the PK of SI-B001 in cynomolgus monkeys, whose parameters were allometrically scaled to humans for the simulation of human PK profiles. Besides, the anti-tumor efficacy of SI-B001 on different xenografts in tumor-bearing mice was quantitatively described by PK/PD models. The clinical effective doses were predicted by comparing the effective exposure (AUCs) in mice with simulated human AUCs. The clinical effective doses of SI-B001 were predicted to be over 16 mg/kg, 5-7 mg/kg or 5-6 mg/kg per week for colon cancer, head and neck cancer or esophageal cancer, respectively, which may help with the optimization of dose escalation schemes and the selection of indications for SI-B001.

Keywords: Bi-specific antibody; EGFR; Effective dose; HER3; PK/PD.

MeSH terms

  • Animals
  • Antibodies, Monoclonal*
  • Area Under Curve
  • Computer Simulation
  • ErbB Receptors* / metabolism
  • Humans
  • Macaca fascicularis / metabolism
  • Mice
  • Models, Biological


  • Antibodies, Monoclonal
  • EGFR protein, human
  • ErbB Receptors