title: Adaptive Design for a Confirmatory Basket Trial in Multiple Tumor Types Based on a Putative Predictive Biomarker.
abstract: Increasingly, tumors are defined on a molecular basis rather than only on histology, and targeted agents, which address these molecular subtypes, are being approved. This profusion of molecular subtypes creates "rare" diseases as subsets of common cancers, leading to difficulties in enrolling sufficiently large cohorts for confirmatory trials. However, if the molecular subtype is shared across various histologies, these may be pooled into a basket trial. To date, basket trials have been primarily for exploratory early development. In this perspective, we consider qualitative designs for confirmatory basket trials. These confirmatory basket designs will provide patients in niche indications with enhanced access to novel therapies, facilitate development and full approval for niche indications, allow accelerated approval for indications within a basket based on a surrogate endpoint, reduce development cost by combining trials, and enhance the ability of regulatory authorities to evaluate risk and benefit in niche indications.
authors: Departments of Oncology and of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA.
authors: R A
authors: RA
authors: Beckman
authors: Amgen, Thousand Oaks, California, USA.
authors: Z
authors: Z
authors: Antonijevic
authors: American Association for Cancer Research, Office of Science Policy and Government Affairs, Washington, DC, USA.|Current address: Genentech, Washington, DC, USA.
authors: R
authors: R
authors: Kalamegham
authors: Biostatistics and Research Decision Sciences, Merck Research Laboratories, Kenilworth, New Jersey, USA.
authors: C
authors: C
authors: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002986:Clinical Trials as Topic / Q000379:methods*; D017277:Drug Approval; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy; D011237:Predictive Value of Tests; D012107:Research Design; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor