Table 3.
CAR-NK clinical trials.
| Phase | Study period | Target antigens, CAR construct & transfection method | Sources of NK cells | Cancer type | NCT number |
|---|---|---|---|---|---|
| Phase I-II | Jun 2017 - Mar 2023 | CD19-CD28-zeta-2A-iCasp9-IL15 Retroviral vector |
CB | B-lymphoid malignancies (ALL, CLL, NHL) | NCT03056339 |
| Phase II | Mar 2020 – May 2039 | CD19-NKG2D-2B4- CD3ζ-IL-15/R-hnCD16 Lentiviral vector |
iPSC | R/R BCLs and CLL | NCT04245722 |
| Phase I | May 2021 – May 2024 | Construct not disclosed Target CD19 Lentiviral vector |
Haploidentical NK cells | B-cell NHL | NCT04887012 |
| Phase I (Terminated) | Oct 2021 - Dec 2022 | Construct not disclosed Target NKG2DL |
CB | R/R AML | NCT05247957 |
| Phase I | Sep 2022 – Sep 2025 | Construct not disclosed Target CD19 |
CB | B-cell NHL | NCT05472558 |
| Early phase I | Jan 2023 – Dec 2024 | Construct not disclosed Target CD19 |
N/A | R/R diffuse large BCL | NCT05673447 |
| Phase I/IIa | Jun 2022 – May 2034 | Claudin6 CAR-NK expressing IL7/CCL19 and/or scFvs against PD1/CTLA4/Lag3 | PB | CLDN6+ advanced solid tumors | NCT05410717 |
| Early phase I | Oct 2022 – Oct 2024 | Construct not disclosed Target CD123 |
N/A | R/R AML | NCT05574608 |
| Early phase I | Mar 2023 – May 2025 | Construct not disclosed Target CD19 |
N/A | R/R B-cell ALL, BCL, CLL | NCT05739227 |
| Phase I | Dec 2021 - Jun 2024 | Construct not disclosed Target NKG2DL |
N/A | Refractory metastatic colorectal cancer | NCT05213195 |
| Phase I | Jan 2023 – Nov 2023 | Construct not disclosed Target NKG2D |
NK-92 cell line | R/R solid tumors | NCT05528341 |
| Phase I | Dec 2022 – Dec 2024 | Construct not disclosed Target CD19 |
N/A | Adult R/R B-cell hematologic malignancies | NCT05645601 |
| Early phase I | Nov 2020 – Nov 2022 | Construct not disclosed Dual target CD33/CLL1 |
N/A | AML | NCT05215015 |
| Not applicable | Mae 2023 – Sep 2024 | Construct not disclosed Target NKG2D |
N/A | Platinum-resistant recurrent ovarian cancer | NCT05776355 |
| Early phase I | Dec 2021 – Dec 2022 | Construct not disclosed Target 5T4 |
N/A | Advanced solid tumors | NCT05194709 |
| Not applicable | Mar 2023 – Sep 2024 | Construct not disclosed Target NKG2D |
N/A | R/R AML | NCT05734898 |
| Early phase I | Dec 2020 – Dec 2023 | Construct not disclosed Target CD19 |
N/A | R/R NHL | NCT04639739 |
| Early phase I | Mar 2019 – Nov 2021 | Construct not disclosed Target CD22 |
N/A | R/R BCL | NCT03692767 |
| Early phase I | Mar 2019 – Nov 2021 | Construct not disclosed Target CD19 |
N/A | R/R BCL | NCT03690310 |
| Phase I | Dec 2021 – Dec 2023 | Construct not disclosed Target CD33 |
N/A | R/R AML | NCT05008575 |
| Early phase I | Nov 2022 – Nov 2023 | Construct not disclosed Target BCMA |
N/A | R/R multiple myeloma | NCT05652530 |
| Early phase I | Mar 2019 – Nov 2021 | Construct not disclosed Target mesothelin |
PB | Ovarian epithelial cancer | NCT03692637 |
| Phase I | Jan 2018 – Dec 2019 | Construct not disclosed Target NKG2DL |
N/A | Metastatic solid tumors | NCT03415100 |
| Phase I | Sep 2022 – Jun 2023 | Construct not disclosed Target DLL3 |
N/A | Extensive stage small cell lung cancer | NCT05507593 |
| Early phase I | Oct 2021 – Sep 2023 | Construct not disclosed Target BCMA |
UB and CB | R/R multiple myeloma | NCT05008536 |
| Phase I Phase II |
May 2019 – May 2022 | Construct not disclosed Target ROBO1 |
N/A | Solid tumor | NCT03940820 |
| Phase I Phase II |
May 2019 – May 2022 | Construct not disclosed Target BCMA |
NK-92 cell line | R/R multiple myeloma | NCT03940833 |
| Phase I | May 2022 – May 2024 | Construct not disclosed Target CD19 |
N/A | ALL, CLL, NHL | NCT05410041 |
| Phase II | Dec 2021 – Dec 2025 | Construct not disclosed Target PD-L1 |
N/A | Recurrent/metastatic gastric or head and neck cancer | NCT04847466 |
| Early phase I | Feb 2019 – Jan 2021 | Construct not disclosed Dual-target CD19/CD22 |
N/A | R/R BCL | NCT03824964 |
| Phase I | Apr 2021 – mar 2024 | Construct not disclosed CD19-IL15 Retroviral vector |
CB | ALL, CLL, NHL | NCT04796675 |
| Phase I | Sep 2020 – Jul 2038 | NKG2D-CD134 (OX40)- CD3ζ -IL-15 | NK cells from haplo-matched donors | R/R AML Refractory myelodysplastic syndromes |
NCT04623944 |
| Phase I | Aug 2021 – Dec 2038 | CD19-CD134 (OX40)-CD3ζ-IL-15 | N/A | R/R NHL, CLL, B cell ALL | NCT05020678 |
| Phase I | Jul 2022 – Nov 2022 | T Construct not disclosed target CD19 |
N/A | R/R ALL | NCT05563545 |
| Completed Phase I Phase II |
Oct 2016 – Sep 2018 | CD33-CD28-CD137 (4-1BB) Lentiviral vector |
NK-92-MI cell line (expressing human IL-2) | R/R CD33+ AML | NCT02944162 |
| Phase I | Dec 2022 – Dec 2025 | CD19/CD70-IL-15 Lentiviral vector |
CB | B cell NHL | NCT05667155 |
| Phase I Phase II |
Sep 2016 – Sep 2019 | CD19-TCRζ-CD28-CD137 (4-1BB) | Allogenic NK-92 cell line | Various subsets of lymphoma | NCT02892695 |
| Phase I Phase II |
May 2019 – May 2022 | Target ROBO1 | N/A | Pancreatic cancer | NCT03941457 |
| Phase I Phase II |
May 2019 – May 2022 | ROBO1 CAR-NK/T cells | N/A | ROBO1+ cancers | NCT03931720 |
| Early phase I | Feb 2023 – Jun 2024 | SZ011 CAR-NK | N/A | Advanced triple-negative breast cancer | NCT05686720 |
| Phase I Phase II |
Dec 2022 – Dec 2024 | Anti-CD19 universal CAR-NK | N/A | B-cell lymphoblastic leukemia/lymphoma | NCT05654038 |
| Early phase I | Dec 2018 – Jun 2024 | Name: TABP EIC Target PSMA |
N/A | Metastatic castration-resistant prostate cancer | NCT03692663 |
| Phase I Phase II |
Oct 2019 – Oct 2019 | CD19-CD28-ζ-2A-iCasp9-IL15 CB-derived |
CB | CD19+ B cell lymphomas | NCT03579927 |
| Phase I | Dec 2022 – Dec 2025 | Construct not disclosed Target CD33 |
Allogeneic NK cells from donors | R/R AML adult | NCT05665075 |
| Phase I | Oct 2022 – Oct 2025 | Construct not disclosed Target CD33 |
Allogeneic NK cells from donors | R/R AML adult | NCT05601466 |
| Phase I | Nov 2021 – Dec 2024 | Construct not disclosed Target CD19 |
NA | B cell ALL | NCT05379647 |
| Phase I | Nov 2021 – Feb 2040 | BCMA-158V CD16-IL-15/IL-15R fusion, CD38-knockout | iPSC | R/R multiple myeloma | NCT05182073 |
| Phase I | Dec 2017 – Dec 2023 | ErbB2-CD28-CD3ζ NK-92/5.28.z |
NK-92 cell line | HER2+ glioblastoma | NCT03383978 |
| Phase I Phase II |
Nov 2022 – Nov 2023 | Construct not disclosed CD70-IL15 |
CB | R/R hematological malignancies | NCT05092451 |
| Phase I | Jan 2023 – Aug 2027 | Construct not disclosed CD19-IL15 |
N/A | R/R CD19+ B-cell malignancies | NCT05336409 |