Table 1.
Some selected and most recent clinical trials (since January 1st 2016) on NK cell-based immunotherapies, in different forms of solid tumors, by using cytokines, monoclonal antibodies (mAbs), and immune checkpoint inhibitors.
| CYTOKINES SUPPORTING NK CELL ACTIVITY | ||||
|---|---|---|---|---|
| Cytokines | In combination with* | Phase | ClinicalTrial.gov identifier | Tumor** |
| IL-15 | – | I | NCT01946789 | M, RCC, NSCLC, HNSCC |
| – | I | NCT01572493 | AST | |
| Ipilimumab and nivolumab | I | NCT03388632 | MeM, RCC, NSCLC, HNSCC | |
| IL-15 superagonist ALT-803 | – | I | NCT02523469 | NSCLC |
| – | I | NCT03054909 | OC | |
| Aldoxorubicin HCl | Ib/II | NCT03563157 | CoC | |
| Ib/II | NCT03387098 | PC | ||
| Ib | NCT03586869 | PC | ||
| I/II | NCT03387085 | TNIBC | ||
| Bacillus Calmette-Guerin | II | NCT03022825 | NMIBC | |
| I/II | NCT02138734 | NMIBC | ||
| Gemcitabine and nab-paclitaxel | I | NCT02559674 | PC | |
| Anti cancer drugs | I/II | NCT03329248 | PC | |
| I/II | NCT03175666 | TNIBC | ||
| I/II | NCT03136406 | PC | ||
| Nivolumab | I/II | NCT02523469 | NSCLC | |
| Nivolumab or pembrolizumab or atezolizumab or avelumab | II | NCT03228667 | NSCLC, SCLC, UC, HNSCC, MCC, M, RCC, GC, CeC, HC, MI, MRD, CoC | |
| ETBX-011 vaccine | Ib/II | NCT03127098 | TC, CoC, OC, BC, LC, PC | |
| ANTIBODIES REDIRECTING NK CELL ACTIVITY | ||||
| Antibodies | In combination with | Phase | ClinicalTrial.gov identifier | Tumor |
| Anti-ErbB3 (ISU104) | – | I | NCT03552406 | AST, BC |
| Anti-globo H (OBI-888) | – | I/II | NCT03573544 | LAMST |
| Anti-CD40 (JNJ-64457107) | – | I | NCT02829099 | NSCLC, PC, M |
| Anti-CD47 (Hu5F9-G4) | – | I/II | NCT02953782 | CoC |
| Anti-TAMUC1 (gatipotuzumab) | Anti-EGFR (tomuzotuximab) | Ib | NCT03360734 | NSCLC, CoC, BC, GyC |
| Anti-semaforin 4D (pepinemab) | – | I/II | NCT03320330 | OS |
| Anti-OX40 (INCAGNO1949) | – | I/II | NCT02923349 | AST, EC, OC, RCC |
| Anti-GD2 (Ch14.18/CHO) | Nivolumab | I | NCT02914405 | NB |
| Nivolumab + ipilumumab + radiation | I/II | NCT03958383 | M | |
| IMMUNE CHECKPOINT INHIBITORS | ||||
| mAbs targeting PD-1 | ||||
| Pembrolizumab | – | II | NCT03241927 | M |
| – | Ib | NCT03590054 | MeM, HNSCC, UC, NSCLC, LC | |
| – | II | NCT02721732 | AST | |
| – | II | NCT03428802 | LAMST, OC, BC | |
| – | II | NCT03447678 | NSCLC | |
| IL-12 | I | NCT03030378 | AST | |
| Autolous DC-CIK cells | I/II | NCT03190811 | LC, RCC, GC, BlC, PC | |
| Lenalidomide | I | NCT02963610 | Neoplams | |
| Enterococcus gallinarum (MRx0518) | I/II | NCT03637803 | NSCLC, M, RCC, BlC | |
| Toll-like receptor (TLR) agonist (BDB001) | I/II | NCT03486301 | AST | |
| AGEN1884 | I/II | NCT02694822 | AST | |
| Nab-paclitaxel + anti cancer drugs | II | NCT03289819 | BC | |
| TLR9 agonist (AST-008) | I/II | NCT03684785 | MeM, HNSCC, SCC, MCC | |
| Poly ICLC | I | NCT02834052 | CoC | |
| Toripalimab | – | I | NCT02857166 | Neoplasms |
| – | I | NCT03713905 | Neoplasms | |
| – | I | NCT03474640 | GC, NC, HC, EsC, STS, CoS | |
| – | I | NCT02836795 | UrC | |
| Anti-VEGFR (surufatinib) | I | NCT03879057 | NeT, LiC, GC | |
| GLS-010 | – | II | NCT03704246 | Neoplasms |
| HX008 | – | I | NCT03468751 | Neoplasms |
| HLX10 | – | I | NCT02715284 | NSCLC, EC, MSI-H |
| TSR-042, dostarlimab | – | I | NCT03286296 | LAMST, NSCLC |
| – | I | NCT02715284 | NSCLC, EC, MSI-H | |
| GB226 | – | I | NCT03374007 | M, NSCLC, RCC, HNSCC, EC, LC, BC |
| INCMGA00012 | – | I | NCT03059823 | LAMST |
| AK105 | – | I | NCT03352531 | AST |
| SG001 | – | I | NCT03852823 | AST |
| CS1003 | – | I | NCT03809767 | Neoplasms |
| SCT-I10A | – | I | NCT03821363 | Neoplasms |
| Sym021 | Anti-LAG3 (Sym022) or anti-TIM3 (Sym023) | I | NCT03311412 | AST |
| Tislelizumab | – | II | NCT03736889 | MSI-H |
| Anti-TIM-3 (BGB-A425) | I/II | NCT03744468 | AST | |
| Anti-TIGIT (BGB-A1217) | I | NCT04047862 | AST | |
| Anti PD-L1 (BGB-A333) | I/II | NCT03379259 | AST | |
| PARP inhibitor (BGB-290) | I | NCT02660034 | AST | |
| Nivolumab | Metformin + rosiglitazone | II | NCT04114136 | RCC, NSCLC, HCC, MSI-H, UC, GC, HNSCC |
| Ipilimumab or BMS-986218 | I/II | NCT03110107 | AST | |
| Ipilimumab | II | NCT02834013 | AST | |
| Anti-TIGIT (BMS-986207) | I/IIa | NCT02913313 | AST | |
| Anti-TIGIT (OMP-313M32) | I | NCT03119428 | Neoplasms | |
| Anti-LAG3 (relatlimab) | I | NCT02966548 | AST | |
| Anti-VEGF (axitinib) | II | NCT03595124 | RCC | |
| Relatlimab + ipilimumab | II | NCT04080804 | HNSCC | |
| Relatlimab or ipilimumab + IDO1 inhibitor (BMS-986205) | I/II | NCT03459222 | LAST | |
| Pembrolizumab + a protein kinase C inhibitor (trigriluzole) | II | NCT03229278 | AST, RCC, HNSCC, NSCLC, BlC, M | |
| Ipilimumab or RGX-104 or docetaxel or pembrolizumab or carboplatin or demetrexed | I | NCT02922764 | AST, NSCLC | |
| Adenoviral product (Ad-p53) + pembrolizumab or capecitabine | I/II | NCT02842125 | AST, HNSCC | |
| Genetically modified HSV for tumor lysis (RP1) | I/II | NCT03767348 | M, BlC, MRD, MSI-H | |
| Avelumab | DC1c (BDCA-1) + myeloid DC + ipilimumab | I | NCT03707808 | Neoplasms |
| Anti-EGFR (cetuximab) + irinotecan | II | NCT03608046 | CoC | |
| ABBV-181 | Anti-delta-like 3 protein (rovalpituzumab) or venetoclax | I | NCT03000257 | NSCLC, TNIBC, OC, HC, GC, SCLC, Me, Cho, MCC, HNSCC |
| Sintilimab | IBI310 | I | NCT03545971 | AST |
| Spartalizumab, PDR001 | Adenosine A2A receptor antagonist (NIR178) | II | NCT03207867 | NSCLC, RCC, PC, UC, HNSCC, MSCC, TNIBC, M |
| SHR-1210 | Parp inhibitor (SHR3162) | I | NCT03182673 | AST |
| JNJ 63723283 | Anti-FGFR1-4 | I | NCT03547037 | Neoplasms |
| AGEN2034 | AGEN1884 | II | NCT03894215 | CeC |
| mAbs targeting PD-L1 | ||||
| HLX20 | – | I | NCT03588650 | Neoplasms |
| KN035 | – | I | NCT03248843 | LAMST |
| – | I | NCT03101488 | HC | |
| Atezolizumab | – | I | NCT02862275 | Neoplasms |
| CS1001 | – | Ia/Ib | NCT03312842 | AST |
| MSB2311 | – | I | NCT03463473 | AST |
| SHR-1316 | – | I | NCT03133247 | AST |
| CK-301 | – | I | NCT03212404 | NSCLC, CC, HNSCC, M, RCC, UC, CoC, EC |
| LY3300054 | CHK1 inhibitor (prexasertib) | I | NCT03495323 | AST |
| Durvalumab | Tremelimumab | III | NCT03084471 | Neoplasms |
| Tremelimumab + fulvestrant | II | NCT03430466 | BC | |
| Tremelimumab + azacitidine | Ib/II | NCT03019003 | HNSCC | |
| Tremelimumab + radiation therapy | II | NCT03601455 | BlC | |
| Tremelimumab + stereotactic body radiotherapy | Ib | NCT03275597 | NSCLC | |
| Tremelimumab + metronomic vinorelbine | I/II | NCT03518606 | BC, HNSCC, CeC, PrC | |
| Avelumab | Anti-TNFRSF9 (utomilumab) + anti-OX40 (PF-04518600) + radiation therapy | I/II | NCT03217747 | AST, PrC |
| mAbs targeting CTLA-4 | ||||
| Fc-engineered IgG1 (AGEN1181) | – | I | NCT03860272 | AST |
| Tremelimumab | PARP inhibitor (olaparib) | I/II | NCT02571725 | OC |
| REGN4659 | Cemiplimab | I | NCT03580694 | NSCLC |
| INT230-6 | Anti-PD-1 | I/II | NCT03058289 | M, HNSCC, BC, PC, LiC, CoC, LC, GB, BDC, OC, SCC |
| Ipilimumab | Oncolytic virus vaccine (pexa-Vec) | I | NCT02977156 | Neoplasms |
| SHR-1210 | I | NCT03527251 | NSCLC | |
| Nivolumab + anti cancer drugs | IIb | NCT03409198 | BC | |
| mAbs targeting TIM-3 | ||||
| Sym023 | – | I | NCT03489343 | AST |
| INCAGNO02390 | – | I | NCT03652077 | CeC, GC, GC, EsC, HC, M, MCC, Me, NSCLC, Oc, HNSCC, RCC, MRD, UC |
| TSR-022 | TSR-042 or anti-LAG3 (TRS-033) | I | NCT02817633 | LAMST, CC, NSCLC |
| LY3321367 | LY3300054 | I | NCT03099109 | AST |
| BGB-A425 | Tislelizumab | I/II | NCT03744468 | LAST |
| BISPECIFIC mAbs | ||||
| Anti-PD-1/anti-LAG3 (MDG013) | Anti-HER2 (margetuximab) | I | NCT03219268 | Neoplasms |
| Anti-PD-1/anti-TIM3 (RO7121661) | – | I | NCT03708328 | MeM, NSCLC, SCLC |
| Anti-PD-1/anti-CTLA-4 (AK104) | Oxaliplatin + capecitabine | I/II | NCT03852251 | GC |
| Anti-PD-1/anti-CTLA-4 (MGD019 DART) | – | I | NCT03761017 | AST |
| Anti-PD-L1/anti-TIM3 (LY3415244) | – | I | NCT03752177 | AST |
| Anti-CTLA-4/anti-OX40 (ATOR-1015) | – | I | NCT03782467 | AST |
| Anti-CTLA-4/anti-LAG3 (XmAb®22841) | Pembrolizumab | I | NCT03849469 | AST |
| Anti-HER2 (MBS301) | – | I | NCT03842085 | BC, SC |
| Anti-GD2/anti-CD3 (hu3F8-BsAb) | – | I/II | NCT03860207 | NB, OS |
| Fusion protein | ||||
| Anti-PD-L1/TGFβRII (M7824) | – | I/II | NCT03436563 | MSI-H RC, CoC |
Immune checkpoint inhibitors reported in the column indicating the “combination” treatment: ipilimumab, pembrolizumab, AGEN1884, IBI310, tremelimumab, BMS-986218: anti-CTLA-4; nivolumab, pembrolizumab, TRS-042, tislelizumab, cemiplimab: anti-PD-1; atezolizumab, avelumab, durvalumab, LY3300054: anti-PD-L1.
Abbreviation of solid tumors: AR, adenocarcinoma of rectum; AST, advanced solid tumors; BC, Breast Cancer; BlC, bladder cancer; BDC, bile duct cancer; BTC, biliary tract cancer; CeC, Cervical Cancer; Cho, cholangiocarcinoma; CoC, Colorectal Cancer; CoS, chondrosarcoma; EC, endometrial cancer; EsC, esophageal cancer; ES, Ewing's sarcoma; ESCC, esophageal squamous cell carcinoma; FTC, fallopian tube cancer; GC, Gastric Cancer; GyC, gynecological cancers; GB, glioblastoma, HC, Hepatocellular Carcinoma; HNSCC, Head and Neck Squamous Cell Carcinoma; HRM, high risk melanoma; LAMST, locally advanced or metastatic solid tumors; LaC, laryngeal cancer; LC, Lung Cancer; LiC, liver cancer; M, Melanoma; MCC, Merkel Cell Carcinoma; MGB, malignant glioma of brain; Me, mesothelioma; MEC, metastatic esophageal cancer; MeM, metastatic melanoma; MI, Microsatellite Instability; MRD, Mismatch Repair Deficiency; MSC, metastatic solid cancer; MSCC, microsatellite stable colon cancer; MSI-H, non-endometrial deficient mismatch repair (dMMR)/microsatellite instability-high; NC, nasopharyngeal carcinoma; NeT, neuroendocrine tumors; NB, neuroblastoma; NMIBC, non-muscle invasive bladder cancer; NSCLC, Non-Small Cell Lung Cancer; OC, Ovarian Cancer; OS, osteosarcoma; PC, Pancreatic Cancer; PDCC, pancreatic ductal cell carcinoma; PhC, pharyngeal cancer; PPC, primary peritoneal cancer; PrC, prostate carcinoma; RCC, Renal Cell Carcinoma; RS, rhabdomyosarcoma; SC, stomach cancer; SCC, squamous cell carcinoma; SCLC, Small Cell Lung Cancer; STS, soft tissue sarcoma; TC, Thyroid Cancer; TNIBC, triple-negative invasive breast carcinoma; ToC, tongue cancer; UC, Urothelial Carcinoma; UrC, urological cancer. Abbreviation of cells: DCs, dendritic cells; CIK, Cytokine-induced killer cells.