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Table 3 Clinical trials for established NK cell-related therapies

From: Natural killer cells in cancer biology and therapy

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
  1. 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