Characteristics of Registered Studies of Chimeric Antigen Receptor Therapies

Abstract

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 optimizationfocused 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.

Rationale and design of the Cancer Immunotherapy Evidence Living (CIEL) Library: A continuously updated clinical trial database of cancer immunotherapies

“…In 2018, 1388 new trials were initiated across all types of immunotherapies for cancer, and in 2022 this number rose to 2095 new trials (5,6). The most prolific immunotherapeutic option is CAR T-cells with, in December 2020, 778 trials registered on ClinicalTrials.gov (7). The US Food and Drug Administration (FDA) approved six CAR-T cell products for different lymphoma, multiple myeloma, and leukemia indications between 2017 and 2022 (8).…”

Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma—Challenges and Potential Solutions

“…However, it is important to discuss the multiple challenges that face patients and their treating oncologists when considering patients for CAR T-cell therapy and put the initial results into perspective. Most CAR T-cell clinical trials thus far have been nonrandomized single-arm studies, and only 1% of CAR T-cell clinical trials (n = 10) were randomized against the standard of care . Single-arm CAR T-cell clinical trials have been subject to selection and reporting bias.…”