Table 2 ∣.
Selected clinical trials of nK cell engagers and nK cell-directed cytokine therapies
| agent | Treatment approach |
Malignancy | Study phase (status) |
ClinicalTrials.gov identifier (trial name) |
|---|---|---|---|---|
| NK cell-engager molecules | ||||
| GTB-3550 (CD16/ IL-15/CD33 TriKE) | Monotherapy | CD33+ high-risk myelodysplastic syndrome, R/R AML or advanced-stage systemic mastocytosis | I/II (recruiting) | NCT03214666 |
| AFM13 (tetravalent bi-specific chimeric anti-CD30/CD16a antibody) | Monotherapy | R/R CD30+ peripheral T cell lymphoma or transformed mycosis fungoides | II (recruiting) | NCT04101331 (REDIRECT) |
| Monotherapy | R/R CD30+ Hodgkin lymphoma | I (completed) | NCT01221571 | |
| In combination with pembrolizumab (anti-PD-1 antibody) | R/R CD30+ Hodgkin lymphoma | I (completed) | NCT02665650 (KEYNOTE- 206) | |
| DF1001 (anti-HER2 TriNKET) | Monotherapy or in combination with pembrolizumab | Advanced-stage HER2+ solid tumours | I/II (recruiting) | NCT04143711 |
| Cytokine-based treatments | ||||
| N-803 (IL-15 superagonist) | Monotherapy | Advanced-stage melanoma, non-small-cell lung carcinoma, renal cell carcinoma or head and neck squamous cell carcinoma | I (completed) | NCT01946789 |
| Subcutaneous recombinant IL-15 | Following infusion of IL-15-activated haploidentical NK cells | R/R AML | II (completed; has results) | NCT02395822 |
| NIZ985 (soluble IL-15/IL-15 receptor-α heterodimer (hetIL-15)) | In combination with spartalizumab (anti-PD-1 antibody) | Solid tumours, lymphoma or melanoma | I/Ib (recruiting) | NCT04261439 |
Owing to the large number of trials in each category, example trials have been selected to illustrate the research and trials mentioned in this Review. Example trials have been selected for larger cohort size, trial status (preference for active trials) and a focus on therapies that most directly test modalities affecting NK cell function in vivo (excluding trials testing multiple agents simultaneously). Studies with an unknown status, or that have been suspended, terminated or withdrawn without results have been omitted from this list. AML, acute myeloid leukaemia; NK, natural killer; R/R, relapsed and/or refractory; TriKE, tri-specific killer engager; TriNKET, tri-specific NK cell engagement therapy.