Related Experiment Video
Updated: Oct 29, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Characteristics of Registered Studies of Chimeric Antigen Receptor Therapies: A Systematic Review
Rahul Banerjee1, Vinay Prasad2,3
1Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco.
Importance:
Hundreds of chimeric antigen receptor (CAR) therapies are under investigation for hematologic malignant cancers and solid malignant tumors. As the field of modern CAR therapy enters its second decade, clinical trials that demonstrate the efficacy of CAR therapies using randomized clinical trials (RCTs) and/or investigate methods to optimize patient outcomes with commercially available CAR therapies are increasingly important.
Objective:
To analyze the landscape of registered CAR-related trials with dual focuses on trial methods and intent.
Evidence Review:
This systematic review identified 1304 ongoing or upcoming CAR-related trials registered at ClinicalTrials.gov as of December 22, 2020, and excluded 513 trials that did not pertain to cell-based therapy. Both CAR-related and trial-related variables, including target antigens and countries of origin, were recorded. Trials were categorized as non-RCTs that compared CAR with non-CAR therapies or RCTs in which every arm received CAR therapy. Trial intent was separately categorized as demonstrating the efficacy of a CAR therapy, optimizing patient outcomes with established CAR therapies using adjunctive non-CAR modalities, or miscellaneous.
Findings:
Of 778 relevant trials, 587 (75%) involved blood cancers, whereas 182 (23%) involved solid tumor cancers; the remaining 9 (1%) involved nonmalignant diseases. A total of 433 trials (56%) were from China and 288 from the US (37%). Ten RCTs (1%) compared CAR therapies with non-CAR therapies, including phase 3 RCTs for 4 of 5 CAR therapies (80%) that are currently commercially available. Twenty-eight studies (4%) sought to optimize outcomes with established CAR therapies using non-CAR drugs or radiotherapy, whereas 3 studies (0.4%) sought to optimize supportive care during CAR therapy.
Conclusions And Relevance:
This systematic review found that randomized and optimization-focused trials are comparatively rare within the landscape of ongoing and upcoming CAR-related trials. As the field of modern CAR therapy enters its second decade, additional studies of these characteristics are necessary to strengthen the evidence base for CAR therapy and improve patient outcomes.
Insights
Randomized clinical trials (RCTs) and optimization studies for chimeric antigen receptor (CAR) therapies are rare. More research is needed to strengthen CAR therapy evidence and improve patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trial Design
Background:
- Chimeric antigen receptor (CAR) therapies are a rapidly evolving area of cancer treatment.
- Hundreds of CAR therapies are under investigation for both hematologic and solid tumors.
- The second decade of CAR therapy necessitates robust clinical trial data.
Purpose of the Study:
- To analyze the landscape of registered CAR-related clinical trials.
- To assess the methods and intent of ongoing and upcoming CAR trials.
- To identify trends in trial design and focus.
Main Methods:
- Systematic review of CAR-related trials registered at ClinicalTrials.gov.
- Inclusion of 778 relevant trials after excluding non-cell-based therapies.
- Categorization of trials by design (RCT vs. non-RCT) and intent (efficacy, optimization, miscellaneous).
Main Results:
- The majority of trials (75%) focused on blood cancers, with fewer on solid tumors (23%).
- China (56%) and the US (37%) were the leading countries for registered trials.
- Randomized clinical trials (RCTs) comparing CAR with non-CAR therapies were rare (1%), as were trials optimizing outcomes with established CAR therapies (4%).
Conclusions:
- Randomized and optimization-focused trials are underrepresented in the current CAR therapy research landscape.
- There is a critical need for more rigorous trial designs to validate CAR therapy efficacy.
- Further research is essential to enhance patient outcomes with CAR therapies.
