Master protocols in oncology: Opportunities, challenges, and strategic approaches to design and implementation.

Abstract

e23010 Background: Master protocols, encompassing basket, umbrella, and platform trials, have emerged as innovative frameworks for oncology research. By evaluating multiple therapies, patient subgroups, or tumor types within a single trial structure, these protocols accelerate drug development and optimize resource utilization. Strategic site selection, emphasizing access to diverse patient populations and advanced biomarker testing capabilities, is critical to their success. Key elements of protocol design, such as adaptive features, shared control arms, and pre-defined go/no-go decision criteria, streamline development while addressing regulatory expectations. However, operational and statistical complexities pose significant challenges to implementation. Methods: This study reviews oncology trials utilizing master protocols to identify best practices and common challenges. Focus areas included site selection strategies, incorporation of adaptive designs, and frameworks for go/no-go decision-making during interim analyses. Statistical methodologies were analyzed for controlling Type I and Type II errors while managing multiplicity across multiple arms or cohorts. Operational strategies, including stakeholder collaboration and real-time data monitoring, were assessed for their role in ensuring trial efficiency and regulatory compliance. Results: Master protocols demonstrated significant efficiency gains by reducing trial timelines and the number of patients required through shared control arms and adaptive cohort expansions. Trials that prioritized sites with robust infrastructure, access to biomarker-defined populations, and expertise in handling complex trial designs achieved higher enrollment rates and lower dropout rates. Implementation of pre-specified go/no-go criteria, such as response thresholds or early futility analyses, enabled timely decision-making while maintaining trial integrity. Challenges included managing logistical complexity, ensuring consistent biomarker testing across sites, and aligning with regulatory expectations for adaptive modifications. Conclusions: Master protocols present transformative opportunities for advancing oncology research by enabling efficient evaluation of therapies and patient subgroups. Strategic site selection and rigorous design of go/no-go criteria are essential to their success. Addressing operational and statistical challenges, while fostering early engagement with regulatory authorities, will be key to fully realizing the potential of master protocols in delivering innovative cancer treatments.