Table 2.
Summary of clinical trials targeting Toll-like receptor (TLRs) as monotherapy or in combination with other treatments.
| TLR targets | Drug name | Combining therapy | Drug name | Indications | Phase | Last report status | NCT number | Myeloid-derived suppressor cell as outcome measure |
|---|---|---|---|---|---|---|---|---|
| TLR 1/2 | XS15 (agonist) | Vaccine | Personalized multi-peptide vaccine | Advanced solid and hematological malignancies | Not applicable | Available | NCT05014607 | No |
| XS15 (agonist) | Vaccine | Multi-peptide vaccine | Leukemia | I | Recruiting | NCT04688385 | No | |
| TLR 3 | Poly-ICLC (agonist) | Vaccine | CDX-1140,6MHP and NeoAg-mBRAF | Melanoma | I/II | Recruiting | NCT04364230 | No |
| Poly-ICLC (agonist) | Vaccine | NY-ESO-1 protein vaccination | Melanoma | I/II | Completed | NCT01079741 | No | |
| Poly-ICLC (agonist) | Cell infusion | GM-CSF+ CAR-T or TCR-T | Gliomas | I | Unknown | NCT03392545 | No | |
| TLR 2/4 | CX-01 (inhibitor) | Chemotherapy | Azacitidine | Leukemia | I | Completed | NCT02995655 | No |
| TLR 4 | GLA-SE (agonist) | Radiotherapy | Sarcoma | I | Completed | NCT02180698 | No | |
| GLA-SE (agonist) | Vaccine | MART-1a peptide or antigen Vaccines | Melanoma | I | Completed | NCT02320305 | No | |
| TLR 5 | Entolimod (agonist) | Monotherapy | Colorectal cancer | II | Unknown | NCT02715882 | No | |
| Entolimod (agonist) | Monotherapy | Advanced solid tumors | I | Completed | NCT01527136 | No | ||
| TLR 7 | 852A (agonist) | Monotherapy | Breast, ovarian, endometrial and cervical cancers | II | Completed | NCT00319748 | No | |
| Imiquimod (agonist) | Monotherapy | Oral cancer | I | Recruiting | NCT04883645 | No | ||
| Imiquimod (agonist) | Chemotherapy | Topical fluorouracil | Cervical intraepithelial neoplasia | I | Active, not recruiting | NCT03196180 | No | |
| Imiquimod (agonist) | Chemotherapy + radiotherapy | Cyclophosphamide | Breast cancer | II | Completed | NCT01421017 | No | |
| Imiquimod (agonist) | Laser therapy | Melanoma | I | Completed | NCT00453050 | No | ||
| NJH395 (agonist) | Anti-HER2 antibody | Non-breast HER2+ advanced malignancies | I | Completed | NCT03696771 | No | ||
| TQ-A3334 (agonist) | Small molecule kinase inhibitor | Anlotinib | Non-small cell lung cancer | I/II | Unknown | NCT04273815 | No | |
| TLR 8 | Motolimod (agonist) | Chemotherapy | Doxorubicin or paclitaxel | Ovarian epithelial, fallopian tube, or peritoneal cavity cancer | I | Completed | NCT01294293 | No |
| Motolimod (agonist) | Chemotherapy | Cyclophosphamide | Metastatic, persistent, recurrent, or progressive solid tumors | I | Terminated | NCT02650635 | Yes | |
| Motolimod (agonist) | Small molecule kinase inhibitor | Cetuximab | Squamous cell cancer of head and neck | I | Completed | NCT01334177 | No | |
| Motolimod (agonist) | Small molecule kinase inhibitor + chemotherapy | Cisplatin or carboplatin + 5-fluorouracil + cetuximab | Squamous cell carcinoma of the head and neck | II | Completed | NCT01836029 | No | |
| TLR 7/8 | BDB001 (agonist) | Monotherapy | PD-(L)1 refractory solid tumors | II | Active, not recruiting | NCT04819373 | No | |
| Resiquimod (agonist) | Vaccine | Gp100(g209-2M) and MAGE-3 vaccines, | Melanoma | II | Completed | NCT00960752 | No | |
| Resiquimod (agonist) | Vaccine | NY-ESO-1 protein vaccination | Tumors express NY-ESO-1 | I | Completed | NCT00821652 | No | |
| TLR 3 or TLR 7/8 | Poly-ICLC (agonist) or resiquimod (agonist) | Vaccine | Peptide vaccine (LPV7) + tetanus peptide | Melanoma | I/II | Unknown | NCT02126579 | No |
| Poly-ICLC (agonist) or resiquimod (agonist) | Vaccine | Tumor-lysate pulsed DC vaccination | Brain tumors | II | Active, not recruiting | NCT01204684 | No | |
| TLR 9 | Tilsotolimod (agonist) | Monotherapy | Melanoma | II | Recruiting | NCT04126876 | No | |
| CpG-STAT3 siRNA CAS3/SS3 (agonist) | Radiotherapy | B-Cell non-Hodgkin lymphoma | I | Recruiting | NCT04995536 | No | ||
| CPG-7909 (agonist) | Radiotherapy | Lymphomas | I/II | Completed | NCT00185965 | No | ||
| CpG-7909 (agonist) | Vaccine | Tumor specific epitope peptides vaccine | Esophageal cancer | I/II | Unknown | NCT00669292 | No | |
| DUK-CPG-001 (agonist) | Cell infusion | NK cell-enriched donor lymphocyte infusions | Myeloid malignancies or lymphoid malignancies | II | Recruiting | NCT02452697 | No | |
| SD-101 (agonist) | Small molecule kinase inhibitor | Ibrutinib | Follicular lymphoma | Ib/II | Active, not recruiting | NCT02927964 | No | |
| EMD 1201081 (agonist) | Small molecule kinase inhibitor | Cetuximab | Head and neck squamous cell carcinoma | II | Completed | NCT01040832 | No | |
| TLR 7,8, and 9 | IMO-8400 (antagonist) | Monotherapy | Diffuse large B cell lymphoma | I/II | Completed | NCT02252146 | No |
The bold entries mean that they are the clinical trials taking MDSCs as outcome measure.