Table 3.
Clinical trials for established NK cell-related therapies
| Mechanism | Condition | Intervention | Phase | Trial identifiers |
|---|---|---|---|---|
| IL-15 signal pathway | Metastatic malignant melanoma, RCC | Recombinant human interleukin-15(rIL-15) | I (first-in human) | NCT01021059 |
| Advanced metastatic solid tumor | IL-15 by continuous infusion | I | NCT01572493 | |
| Refractory and relapsed adult T cell leukemia | IL-15 + alemtuzumab (anti-CD52) | I | NCT02689453 | |
| Refractory and relapsed chronic lymphocytic leukemia | IL-15+ obinutuzumab (anti-CD20) | I | NCT03759184 | |
| Hematologic malignancies recurring after transplantation | ALT-803 (IL-15 superagonist) | I (first-in human) | NCT01885897 | |
| Metastatic NSCLC | ALT-803 + Nivolumab (anti-PD-1 antibody) | Ib | NCT02523469 | |
| IL-21 signal pathway | Relapse/refractory low-grade B-cell LPD | Recombinant human interleukin-21 (rIL-21) + Rituximab (anti-CD20 antibody) | I | NCT00347971 |
| Metastatic malignant melanoma, RCC | rIL-21 | I | NCT00095108 | |
| Stage IV malignant melanoma without prior treatment | rIL-21 | IIa | NCT00336986 | |
| IL-12 signal pathway | Metastatic solid tumors | NHS-muIL12 (two IL12 heterodimers fused to the NHS76 antibody) | I (first-in human) | NCT01417546 |
| Murine mammary/subcutaneous tumors | NHS-muIL12+ Avelumab (anti-PD-L1 antibody) | Preclinical models | – | |
| IL-2 signal pathway | Locally advanced or metastatic solid tumors | NKTR-214 (IL-2 pathway agonist) | I/II | NCT02869295 |
| Advanced Solid Tumors (Japanese) | NKTR-214 + Nivolumab | I | NCT03745807 | |
| Anti-KIR antibody | AML in FCR | IPH2101 (anti-KIR antibody) | I | EUDRACT 2005–005298-31 |
| Relapsed/refractory MM | IPH2101 | I | NCT00552396 | |
| Smoldering MM | IPH2101 | II | NCT01248455 | |
| Relapsed/Refractory MM | IPH2101+ lenalidomide (immunomodulatory agent) | I | NCT01217203 | |
| AML | Lirilumab (2nd generation anti-KIR antibody)) | II | NCT01687387 | |
| SCCHN | Lirilumab + Nivolumab | II | NCT03341936 | |
| Cisplatin-ineligible muscle-invasive bladder cancer | Lirilumab + Nivolumab | Ib | NCT03532451 | |
| Anti-NKG2A antibody | Advanced gynecologic malignancies | Monalizumab (IPH2201, anti-NKG2A antibody) | I | CCGT-IND221 |
| metastatic microsatellite- stable colorectal cancer | Monalizumab + durvalumab | First-in human | NCT02671435 | |
| recurrent or metastatic head and neck cancer | Monalizumab + cetuximab | I | NCT02643550 | |
| TNF pathway | Advanced solid tumors | BMS-986156 (glucocorticoid-induced TNF Receptor-Related Protein Agonist) +/− Nivolumab | I/IIa | NCT02598960 |
| Cell adoptive therapy | Canine sarcomas | Radiotherapy+ intra-tumoral autologous NK transfer | first-in-dog | – |
| Recurrent medulloblastoma and ependymoma (children) | ex-vivo-expanded NK cells | I | NCT02271711 | |
| Metastatic gastrointestinal carcinoma | Adoptive transferred autologous NK cells + cetuximab | I | NCT02845999 | |
| HER2-positive cancers | Adoptive transferred autologous NK cells + trastuzumab | I | NCT02030561 | |
| Locally advanced colon carcinoma | Adoptive transferred autologous NK cells + chemotherapy | I | – | |
| Malignant lymphoma or advanced solid tumors. | Adoptive transferred allogeneic NK cells | I | NCT01212341 | |
| Myeloid leukemia | Adoptively transferred memory-like NK cells induced by IL-12, IL-15, and IL-18 | I (first-in human) | NCT01898793 | |
| High-risk AML, MDS, CML | MbIL21 ex vivo-expanded donor-derived NK cells | I | – | |
| MDS, AML. | Fludarabine/cyclophosphamide + total lymphoid irradiation + adoptive transferred IL2-activated haploidentical NK cells | I | EUDRACT 2011–003181- 32 | |
| Older AML patients | Transferred umbilical cord blood CD34 hematopoietic stem + progenitor-derived NK Cells | I (first-in human) | Dutch clinical trial registry (NTR 2818) | |
| Non-Hodgkin lymphoma | Haploidentical donor NK cells + rituximab+ IL-2 | II | NCT01181258 | |
| Myeloma | α-galactosylceramide-loaded monocyte-derived dendritic cells + low-dose lenalidomide (mediate antigen-specific co-stimulation of human iNKT cells) | I | NCT00698776 | |
| CAR-NK therapy | CD19-positive lymphoid tumors | NK cells expressing anti-CD19 CAR, IL-15 and inducible caspase 9 | I/II | NCT03056339 |
Abbreviation: RCC renal cell cancer, NSCLC non-small cell lung cancer, LPD lymphoproliferative disorders, AML acute myeloid leukemia, FCR first complete remission, MM multiple myeloma, SCCHN squamous cell carcinoma of the head and neck, MDS myelodysplastic syndromes, CML chronic myeloid leukemia