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Updated: Mar 16, 2026
Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances
Published on: October 11, 2018
Adaptive Design for a Confirmatory Basket Trial in Multiple Tumor Types Based on a Putative Predictive Biomarker
R A Beckman1, Z Antonijevic2, R Kalamegham3,4
1Departments 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.
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.
Insights
Molecularly defined cancer subtypes create rare diseases, hindering clinical trials. Basket trials, pooling patients across histologies with shared molecular targets, offer a solution for confirmatory trials, improving access to novel targeted therapies.
Area of Science:
- Oncology
- Clinical Trial Design
- Translational Research
Background:
- Tumor classification is increasingly molecular, leading to targeted therapies.
- Molecular subtypes create rare disease subsets, complicating traditional clinical trial enrollment.
- Basket trials allow pooling patients with shared molecular targets across different cancer histologies.
Purpose of the Study:
- To explore qualitative designs for confirmatory basket trials.
- To address challenges in developing targeted therapies for rare molecular subtypes.
- To enhance patient access to novel treatments in niche oncological indications.
Main Methods:
- Consideration of qualitative research methodologies for confirmatory basket trial design.
- Focus on pooling patient cohorts based on shared molecular alterations across diverse histologies.
- Evaluation of regulatory pathways for accelerated approval using surrogate endpoints.
Main Results:
- Confirmatory basket designs can facilitate development and approval for rare indications.
- These designs improve patient access to novel targeted therapies.
- Combining trials in a basket approach can reduce development costs and aid regulatory review.
Conclusions:
- Qualitative designs offer a viable strategy for confirmatory basket trials.
- Basket trials are crucial for advancing targeted therapy development in rare molecular subtypes.
- This approach enhances regulatory evaluation of risk-benefit for niche cancer indications.
