A Framework for Standardising Toxicity Management Guidelines in Oncology Clinical Trials

Area of Science:

• Oncology
• Clinical Pharmacology
• Drug Development

Background:

• Investigational medicinal products (IMPs) require robust toxicity management guidelines (TMGs) for safe clinical development.
• Antibody-drug conjugates (ADCs) are a rapidly advancing class of oncology drugs necessitating standardized TMGs for clinical trial success.
• Existing TMGs often lack consistency across trials, potentially impacting patient care and risk management.

Purpose of the Study:

• To present a framework for developing standardized TMGs for AstraZeneca's portfolio of antibody-drug conjugates (ADCs).
• To ensure consistent clinical practice and improve patient safety in ADC clinical trials.
• To facilitate early identification and management of potential product-related toxicities.

Main Methods:

• Information gathering from internal documents, published labels, and guidelines.
• Cross-product comparison of toxicity profiles and management strategies within the ADC portfolio.
• Standardization decisions based on biological rationale, study design, and patient context.

Main Results:

• A semi-standardized framework for ADC TMGs was developed, balancing standardization with necessary patient-specific modifications.
• The framework prioritizes patient safety by enabling early intervention and dose adjustments.
• The approach allows for clinical judgment while maintaining a consistent standard of care.

Conclusions:

• Standardized TMGs are crucial for the successful and safe clinical development of ADCs.
• The proposed framework provides a consistent approach to ADC toxicity management across trials.
• The methodology can be adapted for other drug modalities and therapeutic areas, enhancing safety and efficiency in drug development.