[Determining the dose to be injected in the first clinical trials with monoclonal antibodies: not so easy!]

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Monoclonal antibodies (mAbs) are vital oncology therapeutics targeting cancer-specific molecules.
• mAbs generally exhibit low toxicity and lack a direct dose-effect relationship, unlike traditional chemotherapy.
• Current clinical development methods for chemotherapy are inadequate for mAb dose selection.

Purpose of the Study:

• To highlight the challenges in determining optimal dosages for monoclonal antibodies in early clinical trials.
• To underscore the need for novel parameters beyond toxicity for mAb dose selection.
• To address the lack of consensus on appropriate early-phase clinical development strategies for mAbs.

Main Methods:

• Review of existing literature on monoclonal antibody development.
• Analysis of pharmacokinetic and pharmacodynamic principles relevant to biologics.
• Exploration of alternative endpoints for early-phase oncology trials.

Main Results:

• Monoclonal antibodies present unique pharmacokinetic and pharmacodynamic profiles.
• Toxicity is often not the dose-limiting factor for monoclonal antibodies.
• Established dose-finding methodologies for chemotherapy are not directly applicable to mAbs.

Conclusions:

• Novel strategies are required for the effective dose selection of monoclonal antibodies in early clinical development.
• Parameters beyond traditional toxicity assessments are essential for optimizing mAb therapy.
• Further research and consensus-building are needed to define appropriate clinical development pathways for monoclonal antibodies in oncology.