Table 1.
The summary of currently registered clinical trials based on CAR-NK therapy.
| Title | Trial Number (Number of Participants); Phase |
Cancer Type | Treatment; Dosage † | Location |
|---|---|---|---|---|
| Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma * |
NCT03383978 (42); 1 |
Glioblastoma | CAR-NK-92/5.28.z Doses: 1 × 107–1 × 108 CAR-NK cells Ezabenlimab: 240 mg The standard therapy for glioblastoma (radiotherapy and alkylating chemotherapy) allowed until two weeks and Temozolomide allowed up to 48 h prior to the study |
Germany |
| Clinical Research of Adoptive BCMA CAR-NK Cells on Relapse/Refractory MM + |
NCT03940833 (20); 1,2 |
Multiple Myeloma | BCMA CAR-NK 92 cells | China |
| CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma * |
NCT02742727 (10); 1,2 |
Myeloid Leukemia Acute Precursor T-Cell Lymphoblastic Leukemia-Lymphoma T-cell Prolymphocytic Leukemia |
anti-CD7 CAR-pNK cells; The allogeneic NK-92 cell line engineered to contain anti-CD7 attached to TCRzeta, CD28 and 4-1BB signaling domains |
China |
| CAR-pNK Cell Immunotherapy for Relapsed/Refractory CD33+ AML+ |
NCT02944162 (10); 1,2 |
Myeloid Leukemia Acute |
CD33 CAR-NK NK92cells; chimeric antigen receptor NK92 cells transduced with the anti-CD33 vector anti-CD33 CAR-NK (coupled with CD28, CD137 and CD3 zeta signaling domains) |
China |
| NKG2D CAR-NK Cell Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia * |
NCT05247957 (9); 1 |
Myeloid Leukemia Relapsed/Refractory Acute |
NKG2D ligand-specific umbilical cord blood CAR-NK cells Doses: 2 × 106/kg, 6 × 106/kg, 18 × 106/kg CAR-NK cells, Preconditioning: standard chemotherapy |
China |
| NKG2D-CAR-NK92 Cells Immunotherapy for Solid Tumors * |
NCT05528341 (20); 1 |
Solid Tumors Relapsed/Refractory | NKG2D-CAR-NK92 cells; CAR-NK92 cells targeting NKG2D ligands, Doses: 0.5 × 106, 2 × 106/kg |
China |
| NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer * |
NCT05213195 (38); 1 |
Refractory Metastatic Colorectal Cancer | NKG2DL-CAR-NK cells; CAR-NK cells targeting NKG2D ligands, |
China |
| Pilot Study of NKG2D-Ligand Targeted CAR-NK Cells in Patients With Metastatic Solid Tumors + |
NCT03415100 (30); 1 |
Solid Tumors | NKG2DL-CAR-NK cells; CAR-NK cells targeting NKG2D ligands |
China |
| NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS * |
NCT04623944 (90); 1 |
AML, AML Relapsed/Refractory, Adult MDS | NKX101 allogeneic CAR NK cells targeting NKG2D ligands NK cells from haplo-matched related or unrelated donor Doses: 1 × 108 CAR-NK cells (2 × 106/kg for weight < 50 kg), 1.5 × 108 CAR-NK cells (3 × 106/kg for weight < 50 kg) Lymphodepletion: fludarabine/cyclophosphamide or fludarabine/cytarabine (ara-C) |
United States |
| NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers * |
NCT05020678 (60); 1 |
Lymphoma, Non-Hodgkin B-cell Acute Lymphoblastic Leukemia, Large B-cell Lymphoma |
NKX019 allogeneic CAR NK product targeting CD19 on cells. Doses: 3 × 108 NK cells (2 × 106/kg for weight < 50 kg). Lymphodepletion: fludarabine/cyclophosphamide |
United States |
| Anti-CD19 Universal CAR-NK Cells Therapy Combined With HSCT for B Cell Hematologic Malignancies |
NCT05570188 (30); 1,2 (Withdrawn -the principal investigator decides to stop) |
B-cell Lymphoma B-cell Leukemia |
anti-CD19 UCAR-NK cells; Preconditioning: Hematopoietic Stem Cell Transplantation(HSCT) Doses: 5–10 × 106/kg, 1–2 × 107/kg, 2–5 × 107/kg |
China |
| Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia |
NCT05563545 (Completed, November 28, 2023) (21); 1 |
recurrent or refractory CD19 positive acute lymphoblastic leukemia | CAR-NK-CD19 Cells; Doses: 1.0 × 107, 2.0 × 107 and 3.0 × 107 cells /kg, Lymphodepletion: Fludarabine (25–30 mg/kg), Cyclophosphamide (250–300 mg/kg) |
China |
| Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia * |
NCT05410041 (21); 1 |
lymphocyte leukemia, B-cell non-Hodgkin’s lymphoma and chronic B-lymphocyte leukemia | CAR-NK-CD19 Cells; Doses: 1.0 × 107, 2.0 × 107 and 3.0 × 107 cells /kg, Lymphodepletion: Fludarabine (25–30 mg/kg), Cyclophosphamide (250–300 mg/kg) |
China |
| Natural Killer (NK) Cell Therapy for B-Cell Malignancies * |
NCT05379647 (24); 1 |
B-cell Lymphoma B-cell Acute Lymphoblastic Leukemia |
QN-019-a (allogeneic CAR-NK cells targeting CD19) as monotherapy or in combination with Rituximab, Lymphodepletion: Cyclophosphamid, Fludarabine, VP-16 |
China |
| Study of Anti-CD19 CAR NK Cells in Relapsed and Refractory B Cell Lymphoma + |
NCT03690310 (15); 1 |
Refractory B-Cell Lymphoma | anti-CD19 CAR NK Cells; Doses: 50–600 103/kg |
unknown |
| Clinical Study of HLA Haploidentical CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL * |
NCT04887012 (25); 1 |
B-cell Non-Hodgkin Lymphoma | anti-CD19 CAR-NK; lentiviral vector-transduced HLA haploidentical NK cells express anti-CD19 CAR |
China |
| Anti-CD19 CAR NK Cell Therapy for R/R Non-Hodgkin Lymphoma # |
NCT04639739 (9); 1 |
Non-Hodgkin Lymphoma | anti-CD19 CAR-NK; Doses: 2 × 106 /kg, 6 × 106 /kg, 2 × 107/kg Lymphodepletion: Fludarabine (30 mg/m2) Cyclophosphamide (500 mg/m2) |
China |
| Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory B-cell Malignancies * |
NCT05410041 NCT03690310 (9); 1 |
Lymphocytic Leukemia Chronic/Acute Non-Hodgkin Lymphoma |
CAR-NK-CD19 Cells; Derived from allogenic NK cells Doses: 1–3 × 107 /KG, Lymphodepletion: Fludarabine (25–30 mg/kg) Cyclophosphamide (250–300 mg/kg) |
China |
| Allogeneic NK T-Cells Expressing CD19 Specific CAR in B-Cell Malignancies (ANCHOR2) * |
NCT05487651 (36); 1 |
Non-Hodgkin Lymphoma, Relapsed, Adult B-cell Lymphoma B-cell Leukemia |
KUR-502 - transduced allogeneic natural killer T cells against CD19 (CD19.CAR-aNKT cells) Doses: 1 × 107/m2, 3 × 107/m2, 1 × 108/m2. Body surface area (BSA) capped at 2.4 m2. Lymphodepletion: cyclophosphamide (500 mg/m2/day) Fludarabine (30 mg/m2/day) |
United States |
| Study of Anti-CD19/CD22 CAR NK Cells in Relapsed and Refractory B Cell Lymphoma + |
NCT03824964 (10); 1 |
Relapsed/Refractory B-Cell Lymphoma | Anti-CD19/CD22 CAR NK Cells; Doses: 50–600 103 cells/kg |
unknown |
| Study of Anti-CD22 CAR NK Cells in Relapsed and Refractory B Cell Lymphoma + |
NCT03692767 (9); 1 |
Relapsed /Refractory B-Cell Lymphoma | Anti-CD22 CAR NK Cells Derived from allogenic NK cells Doses: 50–600 103 cells /kg |
unknown |
| Study of Anti-CD33/CLL1 CAR-NK in Acute Myeloid Leukemia * |
NCT05215015 (18); 1 |
Myeloid Leukemia Acute |
Anti-CD33/CLL1 CAR-NK Cells; Doses: 2.0 × 109, 3.0 × 109, 3.0 × 109 cells |
China |
| Anti-CD33 CAR NK Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia * |
NCT05008575 (27); 1 |
Leukemia, Myeloid, Acute |
anti-CD33 CAR NK cells; Doses: 6 × 108, 12 × 108, 18 × 108 cells/KG Lymphodepletion: Fludarabine (30 mg/m2) Cytoxan (300–500 mg/m2) |
China |
| Study of Anti-5T4 CAR-NK Cell Therapy in Advanced Solid Tumors * |
NCT05194709 (40); 1 |
Solid Tumors Advanced |
Anti-5T4 Oncofetal Trophoblast Glycoprotein (5T4) Conjugated Antibody Redirecting Natural Killer (CAR-NK) Cells Doses: 3.0 × 109, 4.0 × 109, 4.0 × 109 cells |
China |
| Allogenic CD123-CAR-NK Cells in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia # |
NCT05574608 (12); 1 |
Acute Myeloid Leukemia Refractory/ Recurrent |
Allogenic CD123-CAR-NK cells; Doses: 1 × 106/kg, 5 × 106/kg, 2 × 107/kg Lymphodepletion: Fludarabine, Cyclophosphamide |
unknown |
| Phase I/II Study of CAR.70- Engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Hematological Malignances * |
NCT05092451 (94); 1,2 |
Leukemia, Lymphoma, or Multiple Myeloma | CAR.70/IL15-transduced Cord blood NK cells; Lymphodepletion: Cyclophosphamide Fludarabine phosphate |
United States |
| Anti-BCMA CAR-NK Cell Therapy for the Relapsed or Refractory Multiple Myeloma * |
NCT05008536 (27); 1 |
Multiple Myeloma, Refractory | Anti-BCMA CAR-NK, NK Cells from umbilical cord blood, Doses: 1–3 × 106/KG, 3–6 × 106/KG, 0.6–1.2 × 107/KG Lymphodepletion: Fludarabine (30 mg/m2), Cytoxan (300–500 mg/m2) |
China |
| Cord Blood Derived Anti-CD19 CAR-Engineered NK Cells for B Lymphoid Malignancies * |
NCT04796675 (27); 1 |
Lymphocytic Leukemia Chronic/Acute Non-Hodgkin’s Lymphoma |
Cord blood derived NK cells from healthy donor, transduced with a retroviral vector encoding the anti-CD19 CAR and interleukin-15.CAR-NK-CD19 Cells; Doses: 0.01 × 107, 0.1 × 107, 1.0 × 107/kg Lymphodepletion: fludarabine (30 mg/kg) cyclophosphamide (300 mg/kg) |
China |
| Clinical Study of Cord Blood-derived CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL * |
NCT05472558 (48); 1 |
B-cell Non-Hodgkin Lymphoma | anti-CD19 CAR-NK; Doses: 2.5 × 108 cells,5 × 108 cells, 1 × 109 cells |
China |
| Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances # |
NCT05110742 (48); 1,2 |
Hematological Malignancy |
CAR.5/IL15-transduced cord blood NK cells; Doses: 1 × 107, 1 × 108, 1 × 109, 1 × 1010 cells Lymphodepletion: Cyclophosphamide and Fludarabine or Fludarabine Phosphate |
United States |
| Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies # |
NCT03056339 (36); 1,2 |
B-Lymphoid Malignancies Lymphocytic Leukemia Chronic/Acute Non-Hodgkin Lymphoma |
CAR-NK cells CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer (CB-NK) cells Lymphodepletion: Fludarabine Cyclophosphamide (AP1903 in case of graft-versus-host disease (GvHD) or cytokine release syndrome after the NK cell infusion) |
United States |
| Study of Anti-Mesothelin Car NK Cells in Epithelial Ovarian Cancer + |
NCT03692637 (30); 1 |
Epithelial Ovarian Cancer |
anti-Mesothelin CAR NK Cells; Doses: 0.5–3 × 106/kg cells |
unknown |
| Study of Anti-PSMA CAR NK Cell (TABP EIC) in Metastatic Castration-Resistant Prostate Cancer * |
NCT03692663 (9); 1 |
Metastatic Castration-resistant Prostate Cancer |
TABP EIC (anti-PSMA CAR NK cells) Doses: 0.5, 10, and 30 × 106 CAR NK cells Lymphodepletion: Cyclophosphamide 250 mg/m2, fludarabine 25 mg/m2 |
China |
| CLDN6-CAR-NK Cell Therapy for Advanced Solid Tumors * |
NCT05410717 (40); 1,2 |
Stage IV Ovarian Cancer Testis Cancer, Refractory Endometrial Cancer Recurrent |
CAR-NK cells from patients PMBC; (some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3) |
China |
| Study of DLL3-CAR-NK Cells in the Treatment of Extensive Stage Small Cell Lung Cancer * |
NCT05507593 (18); 1 |
SCLC, Extensive Stage |
DLL3-CAR-NK cells; Doses: 1 × 107, 1 × 108, 1 ×109 DLL3-CAR-NK cells |
China |
| Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer * |
NCT04847466 (55); 2 |
Gastroesophageal Junction (GEJ) Cancers Advanced HNSCC |
Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 Doses: 2 × 109 cells Pembrolizumab 400 mg N-803 (15 mcg/kg) |
United States |
| FT576 in Subjects With Multiple Myeloma * (Allogenic CAR NK cells with BCMA expression) |
NCT05182073 (168);1 |
Multiple Myeloma Myeloma |
FT576 as monotherapy and in combination with the monoclonal antibody daratumumab FT576: allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, iPSC that expresses BCMA, CAR, high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF). Lymphodepletion: Cyclophosphamide Fludarabine |
United States |
| Induced-T Cell Like NK Cellular Immunotherapy for Cancer Lack of MHC-I + |
NCT03882840 (30); 1,2 |
Anti-cancer Cell Immunotherapy T Cell and NK Cell |
Induced-T cell-like NK cells; T-like NK cells (ITNK) from patient’s T cells, |
China |
| Induced-T Cell Like NK Cells for B Cell Malignancies * |
NCT04747093 (12); 1,2 |
B Cell Leukemia B Cell Lymphoma B-cell Acute Lymphoblastic |
CAR-ITNK cells; Induced-T cell-like NK cells with chimeric antigen receptor |
China |
| Clinical Research of ROBO1 Specific BiCAR-NK Cells on Patients With Pancreatic Cancer + |
NCT03941457 (9); 1,2 |
Pancreatic Cancer | BiCAR-NK cells- (ROBO1 CAR-NK cells) Derived from allogenic NK cells |
China |
| Clinical Research of ROBO1 Specific BiCAR-NK/T Cells on Patients With Malignant Tumor + |
NCT03931720 (20); 1,2 |
Malignant Tumor | BiCAR-NK/T cells (ROBO1 CAR-NK/T cells) Derived from allogenic NK cells |
China |
| Clinical Research of ROBO1 Specific CAR-NK Cells on Patients With Solid Tumors + |
NCT03940820 (20); 1,2 |
Solid Tumor | ROBO1 CAR-NK cells; Derived from allogenic NK cells |
China |
* recruiting; # not yet recruiting; + unknown status; † information about pre-condition treatment, type of cells used, and the dosage of CAR-NK cells, if available.