Model-Informed Optimal Dosing of Anti-CD47 Antibody Using Target-Mediated Drug Disposition Model

Area of Science:

• Immunology
• Pharmacology
• Oncology

Background:

• IMC-002 is a fully human IgG4 monoclonal antibody targeting CD47.
• It blocks CD47-SIRPα interactions, promoting cancer cell phagocytosis by macrophages.

Purpose of the Study:

• To establish a target-mediated drug disposition (TMDD) pharmacokinetic (PK) model for IMC-002.
• To use model-informed dosing to optimize the regimen for a Phase 1b study.

Main Methods:

• Analysis of PK data from a Phase 1a dose escalation study in 12 advanced solid tumor patients.
• Utilized NONMEM software (v7.5) with FOCEI for PK analysis.
• Developed a semi-mechanistic TMDD model incorporating FcRn recirculation.

Main Results:

• The TMDD model successfully explained the nonlinear PK properties of IMC-002.
• No significant covariates (weight, sex, age) were identified.
• Simulations identified 20 mg/kg every 3 weeks as the optimal dosing regimen.

Conclusions:

• A robust TMDD PK model for IMC-002 was developed.
• The model provides a strong rationale for the selected dosing regimen in Phase 1b studies.