Table 1 ∣.
Selected ongoing clinical trials of therapeutic NK cell products
| Agent | Cell source |
Treatment approach | Malignancy | Study phase (status) |
ClinicalTrials.gov identifier (trial name) |
|---|---|---|---|---|---|
| CAR NK cells | |||||
| NK-92/5.28.z cells | NK-92 cells | Intracranial injection upon repeat surgery or biopsy | Recurrent HER2+ glioblastoma or gliosarcoma | I (recruiting) | NCT03383978 (CAR2BRAIN) |
| iC9/CD19-CAR-CD28-zeta- 2A-IL-15 NK cells | UCB NK cells | In combination with lymphodepleting chemotherapy | CD19+ R/R B cell malignancies | I/II (recruiting) | NCT03056339 |
| PD-L1-targeted high-affinity NK (PD-L1.t-haNK) | NK-92 cells | NA | R/R advanced-stage solid tumours | I (recruiting) | NCT04050709 (QUILT 3.064) |
| In combination with N-803 | Locally advanced or metastatic pancreatic cancer | II (recruiting) | NCT04390399 (QUILT 88) | ||
| CD19-targeted high-affinity NK (CD19.t-haNK) | NK-92 cells | NA | Diffuse large B cell lymphoma | I (not yet recruiting) | NCT04052061 (QUILT 3.061) |
| Genetically modified NK-92 cells | |||||
| NK cells expressing high-affinity variant of CD16 (haNK) | NK-92 cells | Combined with NANT cancer vaccine, avelumab (anti-PD-L1 antibody) and various other agents | R/R advanced stage triple-negative breast cancer | Ib/II (active, not recruiting) | NCT03387085 (QUILT-3.067) |
| Combined with an IL-15 superagonist (N-803) and avelumab | Merkel cell carcinoma that has progressed after ICI | I (recruiting) | NCT03853317 (QUILT-3.063) | ||
| Combined with NANT cancer vaccine, avelumab and various other agents | Squamous cell carcinoma (of the lung or head and neck) that has progressed after platinum-based chemotherapy and ICI | Ib/II (active, not recruiting) | NCT03387111 (QUILT-3.090) | ||
| Combined with NANT cancer vaccine, avelumab and various other agents | R/R pancreatic cancer | I (active, not recruiting) | NCT03586869 (QUILT-3.080) | ||
| iPSC-derived NK cells | |||||
| FT500 (off-the-shelf iPSC NK cells) | iPSCs | Monotherapy or combination with PD-1–PD-L1 ICI (using nivolumab, pembrolizumab or atezolizumab) | R/R advanced-stage solid or haematological cancer | I (recruiting) | NCT03841110 |
| FT516 (iPSC NK cells expressing high-affinity, non-cleavable CD16 (hnCD16)) | iPSCs | Monotherapy for AML or in combination with anti-CD20 antibodies (rituximab or obinutuzumab) for B cell lymphoma | R/R AML or B cell lymphoma | I (recruiting) | NCT04023071 |
| FT596 (iPSC NK cells expressing an anti-CD19 CAR, hnCD16 and IL-15) | iPSCs | Monotherapy or combination with anti-CD20 antibodies (rituximab or obinutuzumab) | R/R chronic lymphocytic leukaemia or B cell lymphoma | I (recruiting) | NCT04245722 |
| CIML NK cells | |||||
| CIML NK cell infusions | PB NK cells | In combination with IL-2 | Myeloid disease that has relapsed after haploidentical HSCT | I (recruiting) | NCT04024761 |
| After T cell donor lymphocyte infusion |
AML that has relapsed after allogeneic HSCT | I (recruiting) | NCT03068819 | ||
| With IL-2 or N-803 | R/R AML or myelodysplastic syndrome | I/II (recruiting) | NCT01898793 | ||
| With N-803 | R/R AML | II (recruiting) | NCT02782546 | ||
| Adaptive NK cells | |||||
| CMV-MVA Triplex vaccine | NA | Administered on days 28 and 56 after autologous HSCT, in order to enhance adaptive NK cell reconstitution | Lymphoma or multiple myeloma | I (completed) | NCT03383055 |
| Adaptive NK cells (cont.) | |||||
| FATE-NK100 | PB NK cells | Combined with subcutaneous IL-2 | R/R AML | I (active, not recruiting) | NCT03081780 |
| Intraperitoneal delivery with IL-2 | Recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer | I (recruiting) | NCT03213964 | ||
| Monotherapy, or combination with cetuximab (anti-EGFR antibody) or trastuzumab (anti-HER2 antibody) | Advanced-stage solid tumours | I (active, not recruiting) | NCT03319459 | ||
| UCB HPC-derived NK cells | |||||
| UCB NK cells | UCB CD34+ HPC-derived NK cells | With or without low-dose or high-dose subcutaneous IL-2 | R/R AML | I/II (not yet recruiting) | NCT04347616 (NK4AML) |
| Monotherapy by intraperitoneal infusion | Recurrent ovarian carcinomas | I (recruiting) | NCT03539406 (INTRO) | ||
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; CAR, chimeric antigen receptor; CIML, cytokine-induced memory-like; CMV-MVA, cytomegalovirus-modified vaccinia Ankara; HPC, haematopoietic progenitor cell; HSCT, haematopoietic stem cell transplantation; iC9, inducible caspase-9; ICI, immune-checkpoint inhibition; iPSC, induced pluripotent stem cell; NA, not applicable/available; NK, natural killer; PB, peripheral blood; R/R, relapsed and/or refractory; t-haNK, NK-92 cells expressing high-affinity CD16 and a CAR; UCB, umbilical cord blood; zeta, CD3ζ domain.