Table 3 Clinical trials for established NK cell-related therapies

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

–

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