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

Abstract

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.