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Updated: Aug 1, 2026
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Summary of US Food and Drug Administration Chimeric Antigen Receptor (CAR) T-Cell Biologics License Application
Xue Lin1, Shiowjen Lee1, Poornima Sharma1
1Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
Abstract:
The approval of tisagenlecleucel and axicabtagene ciloleucel in 2017 marked a milestone in the development of oncology therapies. Since 2017, the breakthrough in treatment or even cure of previously intractable diseases represented by this new class of cancer treatments has continued with subsequent chimeric antigen receptor T (CAR T)-cell approvals. To date, the US Food and Drug Administration has approved five autologous CAR T-cell products for seven indications. A feature of autologous CAR T-cell products that differentiates them from traditional oncology drugs is that they need to be manufactured specifically for each patient. This feature has implications in study design, statistical analyses, and interpretation of study results. In this article, we share our experiences in the statistical review of CAR T-cell products and provide considerations for the design and statistical analyses of CAR T-cell trials. We also describe how the newly adopted estimand framework for clinical trials can help clarify nuanced issues in CAR T-cell trial design.
Insights
Chimeric antigen receptor T (CAR T)-cell therapies offer new hope for intractable diseases. Statistical review of these personalized treatments requires specific considerations for trial design and analysis.
Area of Science:
- Oncology
- Immunotherapy
- Biostatistics
Background:
- Tisagenlecleucel and axicabtagene ciloleucel approvals in 2017 revolutionized oncology.
- Subsequent chimeric antigen receptor T (CAR T)-cell approvals demonstrate continued breakthroughs in treating intractable diseases.
Purpose of the Study:
- To share experiences in the statistical review of autologous CAR T-cell products.
- To provide considerations for designing and statistically analyzing CAR T-cell trials.
- To describe the utility of the estimand framework in CAR T-cell trial design.
Main Methods:
- Review of statistical methodologies applied to CAR T-cell product development.
- Discussion of unique challenges posed by patient-specific manufacturing.
- Application of the estimand framework to clarify trial design and analysis issues.
Main Results:
- Autologous CAR T-cell products require unique approaches to study design and statistical analysis.
- The estimand framework offers a structured method for addressing complexities in CAR T-cell trials.
- Five autologous CAR T-cell products have been approved by the FDA for seven indications.
Conclusions:
- Statistical review of CAR T-cell therapies necessitates specialized considerations due to their personalized nature.
- The estimand framework is a valuable tool for enhancing the rigor of CAR T-cell clinical trial design and interpretation.
- Continued advancements in CAR T-cell therapy underscore the importance of robust statistical methodologies.
