Immune effector cell therapies in oncology: A systematic analysis and forecast from ClinicalTrials.gov.

Abstract

e14516 Background: IEC are arguably the most promising therapy in oncology, and FDA approvals for CAR T cells are a testament to their real potential. This has led to a great growth of clinical trials (CT), making the evaluation of their associated data increasingly challenging. To facilitate this process, we performed a systematic review of ClinicalTrials.gov focused on IEC therapies in oncology. We performed an analysis of the CT data and forecast trends for 2025. Methods: CT registries were retrieved from ClinicalTrials.gov with a systematic search query. We included CT registered between 1993-2020, which used IEC-based therapies in oncology. Statistical analysis using descriptive and inferential methods allowed us to identify trends and establish forecasts. Results: We identified 938 registrations of IEC-CTs in oncology, and 51% of those were active. The most common IEC type was CAR T (51%), followed by NK (15%), TCR T (8%), TIL (8%), and CIK (3%). 69% of IEC-CTs were aimed at a specific target vs. 31% that lack that specificity. The number of annual CAR T-CTs continue to increase, and we forecast 320 registrations during 2025. Since 2018, the number of CTs using unmodified T cells and TIL has increased (largely due to metastatic melanoma studies). NK cells CTs represent 8% of all registrations, and by 2025 we anticipate that >150 NK-based CTs will be registered per year, a number similar to CAR T-CTs registered during 2020. IEC-CTs based on allogeneic sources represent 18% of all registrations and are expected to grow 2.5 fold in the next 5 years. In solid tumors, the most common IEC-CTs are based on Non-CAR studies, while in hem-malignancies 76% of CTs are CAR T. Only one solid tumor, CAR T-CT, has reached phase 2/3, while 7 CIK-CTs were used to target various organ tumors. Conclusions: IEC-CTs continue to grow exponentially and represent an active field of clinical research in oncology. Allogeneic and NK-CTs increase rapidly and are among the most promising IEC-CTs. A rising proportion of CTs in solid tumors are using CIK and TIL rather than CAR T-cells, which are more popular for treating hem-malignancies. This is a direct reflection of the challenges associated with CAR T infiltration and persistence in solid tumors. Our analyses indicate that annual IEC-CTs registrations will double by 2025. We anticipate the increase in cellular therapy options will demand an organized response, including adequate logistical planning and policy implementation in response to the landscape changes in clinical oncology during the upcoming years.[Table: see text]