Advancing Immunology Research Through Early Phase Basket Trials

This white paper examines the methodological, operational, and regulatory aspects of basket trial designs applied to immune-mediated disorders. It discusses how these trials utilize shared biomarkers and overlapping pathophysiology to enhance signal detection and proof of concept, potentially streamlining resource use compared to traditional indication-specific trials. The paper outlines the challenges associated with basket trials, including analytical complexity, limited clinical inference due to small cohorts, and varying regulatory expectations. It emphasizes the necessity for strong mechanistic justification, predefined borrowing and multiplicity strategies, early engagement with regulatory agencies, and a robust operational infrastructure to ensure success. The paper also highlights the advantages of basket trials, such as faster identification of responsive indications and reduced redundancy, while addressing their limitations, including operational challenges and stakeholder resistance. Ultimately, it presents basket trials as a promising translational platform for advancing immunological therapeutics in a mechanism-driven, indication-agnostic framework.