Characterizing clinical trials for CAR T targeting solid tumors from 2018 to 2023: A systematic review.

Abstract

e15080 Background: In the last decade, there have been many advances in the treatment of solid tumors, including new chemotherapy agents, immunotherapy, and most recently, cellular therapies. Chimeric antigen receptor T-cell (CAR T) therapy, first approved for acute lymphoblastic leukemia in 2017, represented a paradigm shift in hematologic malignancies, producing response rates that dramatically outpaced alternative regimens in a relapsed/refractory patient setting. Approvals in large B-cell lymphomas and multiple myeloma followed. Excited by the potential of CAR T, investigators worldwide have initiated trials to investigate the use of CAR T in solid tumors. This review explores the trials conducted globally, evaluating the potential molecular targets and the status of current clinical trials. Methods: This systematic review identified CAR T clinical trials specifically targeting solid tumors starting in 2018 to 2023 registered at ClinicalTrials.gov as of January 8, 2024. Trial-related variables including trial phase, primary trial site location, primary endpoints, start and end dates, and molecular target were captured. Results: We screened 110 clinical trials, ultimately including 103 studies for analysis after excluding trials without a CAR T construct in the methods. The number of new clinical trials increased over time, with a significantly larger increase (440%) seen with non-US sponsors compared to US sponsors (100%), p< 0.0001. Only 19 trials (18%) are/were being conducted in the United States in the studied time period. There were 33 unique molecular targets used, with mesothelin (17%), and the claudin protein family (13%) as the most frequented targets. Conclusions: The success that CAR T has demonstrated in hematologic malignancies has created great hope in solid tumor malignancies, although tempered by differences between the two categories. Unlike hematologic cancers, solid tumors exhibit significant biomarker variation, with interpatient biomarker expression varying greatly, even within the same tissue diagnosis. To deal with this issue, the majority of clinical trials that were reviewed here were not restricted to a single disease location such as breast cancer or esophageal cancer but were rather restricted by the expression of the targeted epitope, to allow for the heterogeneity inherent in these tumors. As presented here, substantial efforts are being made worldwide to improve these technologies, but the United States appears to be lagging in clinical trial efforts, compared to other nations. Further investigation is warranted into this topic, as the usage of CAR T quickly spreads from a therapy only used in hematology to one with promise in solid tumors, infectious diseases, and beyond.