A Framework for Standardising Toxicity Management Guidelines in Oncology Clinical Trials.

Abstract

For new investigational medicinal products (IMPs) entering clinical development, toxicity management guidelines (TMGs) can be developed as an addition to the clinical study protocol. These guidelines inform best clinical practice for the treatment of potential product-related toxicities including dose modifications and symptom management recommendations. TMGs ensure that early identification and intervention strategies are in place, helping to minimise risks and improve patient outcomes. Antibody-drug conjugates (ADCs) are a rapidly evolving drug class within oncology, and their accelerated development should be accompanied by high quality TMGs to support clinical trial success. Having a pre-prepared, 'off-the-shelf' set of TMGs for ADCs ensures consistency of care across several clinical trials investigating this drug class. The authors present a framework for developing these standardised TMGs across AstraZeneca's ADC portfolio. It incorporates information gathering from internal documents and published labels or guidelines, cross-product comparison, and standardisation decisions based on biological rationale and study/patient context. Although patient- and context-specific modifications remain necessary, a semi-standardised framework prioritises safety while allowing clinical judgment. Considerations for specific circumstances when the TMGs could be deviated from and how the approach can be extended to additional modalities and therapy areas are discussed.