Table 4.
Status of clinical trials with TLR agonists for therapeutic intervention of human cancers.
| Targeting TLR | Name of Agonist/Drug | Name of Cancer | Intervention application | Mechanism of action | Clinical trial number |
|---|---|---|---|---|---|
| Active/recruited in PHASE I trial | |||||
| TLR3 | Poly ICLC: Hiltonol | Breast carcinoma | In combination with vaccine, and chemotherapy | Intramuscular application is active; endogenous type I IFN inducer. | NCT02826434 |
| NCT03362060 | |||||
| Glioma | In combination with vaccine (peptide) and surgery | Subcutaneous application is active; Induction of CD8+ T-cell responses. | NCT02960230; | ||
| NCT02924038 | |||||
| NCT02549833 | |||||
| Prostrate cancer | Combination with surgery | Intramuscular recruiting trial; increases IFN-β and IFN-α expression in the circulating PBMCs. | NCT03262103 | ||
| Multiple myeloma | Combination with vaccine and chemotherapy | Recruited in the trial; high degree of T cell response. | NCT02886065 | ||
| TLR 7 | Imiquimod: R837, Aldara, UGN-201 | Bladder cancer | Combination with surgery and drugs | Intravesical recruiting trial | NCT05375903 |
| NCT05055050 | |||||
| Squamous cell carcinoma | Combination with chemotherapy | Topical recruiting trial | NCT03370406 | ||
| Solid tumors | Combination with vaccine and drugs | Topical recruiting trial | NCT04116320 | ||
| NCT03872947 | |||||
| Oral cancer | Single-use drug | Topical, recruiting trial | NCT04883645 | ||
| TLR7/8 | BDB001 | Solid tumors | Single-use in combination with drug | Recruited in the trial. | NCT03486301 |
| NCT04196530 | |||||
| TLR9 | SD-101 | Solids tumors | Combination with BMS 986178 | Intratumoral application is active. | NCT03831295 |
| Lymphoma | Combination with radiotherapy and | Intratumoral application is active. | NCT03410901 | ||
| Pancreatic adenocarcinoma | Combination with Nivolumab and radiation | Intratumoral application is active. | NCT04050085 | ||
| CMP-001:Vidutolimod, ARB- 1598; CMP-001: CYT-003 |
Colorectal cancer | Combination with Nivolumab, Ipilimumab and Radiotherapy | Subcutaneous and/or intratumoral application is active. | NCT03507699 | |
| Completed PHASE I trial | |||||
| TLR3 | Poly ICLC: Hiltonol | Acute myeloid leukemia, myelodysplastic syndrome |
In combination with vaccine and chemotherapy | Induces expression of tumor antigen and induces cytotoxic T cells. |
NCT01834248 |
| NCT03358719 | |||||
| Solid tumors | Vaccine adjuvants; chemotherapeutic drug combinations | Elicits innate and humoral immune responses; increases tumor-infiltrating T cells. | NCT02721043 | ||
| NCT02897765 | |||||
| NCT02544880 | |||||
| Pancreatic cancer | vaccine | Elevates the intensity and duration of the immune responses. | NCT01677962 | ||
| Lungs cancer | vaccine | Activation of anti-tumor immune responses. | NCT03380871 | ||
| Melanoma | vaccine | Increased T cell response in synergy with vaccine candidate. | NCT01585350 | ||
| TLR4 | LPS | Melanoma | vaccine | Induces immune-responses and immunogenicity. | NCT01585350 |
| GLA-SE: G100 | Merkel cell carcinoma | In combination with Surgery and radiotherapy | Less toxicity and efficient clinical acceptability. | NCT02035657 | |
| Melanoma | vaccine | Effective vaccine adjuvant and increased immunopotency of vaccine. | NCT01585350 | ||
| Sarcoma | In combination with Radiotherapy | Ameliorates local sarcoma and induces proliferation of CD4+ T cell response. | NCT02180698 | ||
| GSK1795091 (CRX-601) | Solid tumors | Intravenous administration with immunoadjuvants | Inhibition of tumor growth with no adverse side effects. | NCT02798978 | |
| TLR5 | entolimod | solid tumors | Intramuscular/subcutaneous single use | Reduces local tumorogenic responses. | NCT01527136 |
| TLR7 | Imiquimod | gastric cancer and breast cancer |
In combination with Vaccine and chemotherapy | Topical application elevates anti-cancer immune responses. | NCT02276300 |
| Glioma | In combination with Vaccine | Stimulate immune responses by increasing the proliferation of IL-17 and IDH1 specific T cells. | NCT02454634 | ||
| Prostrate cancer | Vaccine | Induces strong immunogenic response. | NCT02293707 | ||
| TLR7/8 | Resiquimod: R848; S28463 | Melanoma | Vaccine | Elicits humoral and CD4+ T cell responses. | NCT00821652 |
| TLR8 | Motolimod: VTX-378, VTX- 2337 |
Ovarian tumors | In combination with chemotherapy | Disease stabilization and amelioration of tumor. | NCT01294293 |
| TLR9 | CMP-001: Vidutolimod | Lungs carcinoma | In combination with Radiotherapy | Reduces disease burden. | NCT03438318 |
| Active and/or recruiting PHASE II trial | |||||
| TLR3 | Poly ICLC: Hiltonol | Brain tumors | Combination with vaccine | Active in trial | NCT01204684 |
| Melanoma | Intradermal and/or subcutaneous administration as vaccine adjuvant and antibody treatment | Active in trial | NCT02126579 | ||
| NCT04364230 | |||||
| BO-112 | Melanoma | In combination with drugs | Intratumoral application is active | NCT04570332 | |
| TLR7 | Imiquimod (R837, Aldara, UGN-201) | Cervical intraepithelial neoplasia | Single use with vaccine | Recruited in the trial | NCT02864147 |
| Basal cell carcinoma | Combination with surgery and drugs | Recruited in the trial | NCT03534947 | ||
| Resiquimod (R848; S28463) | Brain tumor | Use with vaccine | Active in trial | NCT01204684 | |
| Melanoma | Adjuvant for vaccine | Active in trial | NCT02126579 | ||
| TLR9 | SD-101 | Prostrate carcinoma | Used with radiation | Recruited in the trial | NCT03007732 |
| Tilsotolimod (IMO-2125) | Solid carcinomas | Application with drugs | Active in trial | NCT03865082 | |
| Malignant melanoma | Single application | Recruited in the trial | NCT04126876 | ||
| CMP-001 (Vidutolimod, ARB-1598, CYT-003) | Melanoma | Combination with surgery and drugs | Recruited in the trial | NCT04401995 | |
| NCT04708418 | |||||
| NCT04698187 | |||||
| NCT03618641 | |||||
| Breast cancer (triple negative) | Combination with radiotherapy | Recruiting trials | NCT04807192 | ||
| Completed PHASE II trial | |||||
| TLR3 | Poly ICLC (Hiltonol) | Melanoma | Single application as intratumoral and/or intramuscular | Induce systemic immune response. | NCT02873819 |
| NCT01079741 | |||||
| Solid tumors | Combination with vaccine and drugs | Induction of tumor-specific immune response. | NCT02873819 | ||
| NCT02643303 | |||||
| Rintatolimod (Ampligen, Atvogen) | Metastatic colorectal cancer | Used in chemokine modulation | Elicits anti-tumorigenic response. | NCT03403634 | |
| TLR4 | IDC-G305 | Multiple cancers: melanoma, renal-cell carcinoma, ovarian cancer | Single intramuscular dose | Efficacious therapeutic potential to generate antigen-specific immune response. | NCT02015416 |
| TLR7 | Imiquimod (R837, Aldara) | Stage 2 and 3 Cervical intraepithelial neoplasia | In application with surgery | Endorses the regression of cervical high-grade intraepithelial lesions. | NCT03233412 |
| NCT02130323 | |||||
| Breast cancer | In combination with radiation and chemotherapy | Reduces disease burden | NCT01421017 | ||
| NCT00899574 | |||||
| Prostrate cancer | Used as vaccine and incomplete Freund’s adjuvant | Triggers high immunogenic response. | NCT02293707 | ||
| TLR9 | SD-101 | Solid tumors and lymphoma | applied with drugs and radiotherapy | Enhances antigen-specific immunity. | NCT02254772 |
| NCT03322384 | |||||
| CpG7909 | Mantle cell lymphoma, recurrent lymphoma | In combination with a vaccine, several drugs, and chemotherapy | Induce anti-tumor CD8 T cell immune response to reduce the clinical outcomes. | NCT00490529 | |
| Multiple TLRs: TLR2, 4 and 9 | Bacille CalmetteGuérin (BCG) | Bladder cancer | Applied with vaccine and drugs | Intravesical application triggers anti-tumor immune response | NCT01373294 |
| NCT02015104 | |||||
| NCT02792192 | |||||