Exploring the Landscape of Genetically Modified Natural Killer Cell (GMNKC) Therapies: A Review of Clinical Trials Indexed on ClinicalTrials.gov

OBJECTIVES: This study examined the landscape of GMNKC therapies, including chimeric antigen receptor (CAR) and gene-editing technologies. These emerging therapies hold promise for treating various hard-to-treat cancers. Clinical trial registries, such as ClinicalTrials.gov, serve as crucial sources of information on pipeline products, enabling anticipation of therapies throughout clinical development.

METHODS: In December 2023, a comprehensive search was conducted on ClinicalTrials.gov to identify trials evaluating GMNKC therapies. The search strategy involved keywords and filters to focus on interventional studies while excluding withdrawn, terminated, and early phase 1 studies. The screening process was performed by one researcher and quality checks were conducted by a second researcher.

RESULTS: The search identified a total of 320 trials, with 46 specifically focusing on GMNKC therapies. Most of these trials were early phase, ongoing, single-arm, open-label studies. No phase 3 trials were found. The majority (72%) of these studies commenced in or after 2020 and were primarily conducted in China (67%) or the United States (28%). Industry sponsorship fully or partially supported approximately two-fifths (43%) of these trials. Sample sizes varied across the studies and ranged from 2 to 168 patients. While all trials included both genders, only 13% enrolled children alongside adults. Hematological malignancies constituted the primary focus area (63%), followed by solid tumors (35%). Allogeneic cells were predominantly used as the cell source in most studies (65%), with CD19 being the most targeted receptor (30%), followed by CD33 and NKG2D ligands (9% each). Among those reporting their activity status (n=35), only four trials have been completed. Two did not report results in either clinicaltrials.gov or a publication; results from the other 2 showed promising clinical response.

CONCLUSIONS: The significant number of clinical trials dedicated to investigating GMNKC therapies indicates an active pipeline poised to deliver novel oncologic treatments in forthcoming years.