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    DRUG CLASS:

    TLR3 agonist

    Related drugs:
    7d
    1B-22-2: In Situ Immunomodulation with CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients W/ Unresectable and Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial primary completion date • Immunomodulating • Metastases
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    HER-2 (Human epidermal growth factor receptor 2)
    |
    Keytruda (pembrolizumab) • CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    14d
    A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma (clinicaltrials.gov)
    P1, N=6, Recruiting, Jonsson Comprehensive Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Dec 2024 --> Jun 2024
    Enrollment open • Trial initiation date
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    Hiltonol (poly-ICLC)
    17d
    Enhanced efficacy of a TLR3 agonist delivered by cowpea chlorotic mottle virus nanoparticles. (PubMed, Small Sci)
    We also combined CCMV-poly(I:C) with oxaliplatin and found the combination therapy to be even more potent, strongly inhibiting tumor growth and increasing survival...The combined treatment also enhanced the rate of apoptosis and immunogenic cell death (ICD). Our data support the development of combination therapies involving immunomodulatory plant virus nanoparticles and antineoplastic drugs to attack tumors directly and via the activation of innate and adaptive immune responses.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • IL4 (Interleukin 4)
    |
    oxaliplatin
    24d
    KEYNOTE-A06: Study of BO-112 With Pembrolizumab for Colorectal or Gastric/GEJ Cancer With Liver Metastasis (clinicaltrials.gov)
    P2, N=18, Terminated, Highlight Therapeutics | Phase classification: P2a --> P2
    Phase classification • Combination therapy
    |
    RAS wild-type • EGFR positive
    |
    Keytruda (pembrolizumab) • polyinosinic:polycytidylic acid (BO-112)
    1m
    Neo-adjuvant Evaluation of Glioma Lysate Vaccines in WHO Grade II Glioma (clinicaltrials.gov)
    P1, N=28, Completed, Jennie Taylor | Active, not recruiting --> Completed
    Trial completion
    |
    CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10)
    |
    CXCL10 expression
    |
    GBM6-AD • Hiltonol (poly-ICLC)
    1m
    Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer. (PubMed, J Immunother Cancer)
    Combined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab.
    Journal
    |
    FOXP3 (Forkhead Box P3) • TLR3 (Toll Like Receptor 3) • IFNA1 (Interferon Alpha 1)
    |
    Keytruda (pembrolizumab) • paclitaxel • doxorubicin hydrochloride • cyclophosphamide • Ampligen (rintatolimod) • celecoxib oral
    1m
    Intratumoral administration of poly-ICLC enhances the antitumor effects of anti-PD-1. (PubMed, J Hepatobiliary Pancreat Sci)
    Combination therapy with poly-ICLC, especially through IT route, and anti-PD-1 provides significantly greater antitumor effects than anti-PD-1 monotherapy in syngeneic mouse models of HCC.
    Journal
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma)
    |
    nCounter® PanCancer IO 360™ Panel
    |
    Hiltonol (poly-ICLC)
    1m
    Ampligen Combined With SOC Versus SOC Alone Following First-Line Therapy in Subjects With LAPC (clinicaltrials.gov)
    P2, N=90, Recruiting, AIM ImmunoTech Inc. | Trial completion date: Apr 2028 --> Jul 2028 | Trial primary completion date: Mar 2028 --> Jun 2028
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Ampligen (rintatolimod)
    2ms
    Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV (clinicaltrials.gov)
    P1, N=40, Not yet recruiting, National Institute of Allergy and Infectious Diseases (NIAID)
    New P1 trial
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    CD40 (CD40 Molecule)
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    Hiltonol (poly-ICLC)
    2ms
    Regulatory T cells modulate monocyte functions in immunocompetent antiretroviral therapy naive HIV-1 infected people. (PubMed, BMC Immunol)
    We observed that Treg cells were able to down modulate autologous monocytes activation as well as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production during stimulation with polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC)...Compared to immunosuppressed participants (CD4 < 500 cells/µL), immunocompetent participants (CD4 ≥ 500 cells/µL) showed significantly higher levels of transforming growth factor beta (TGF-β) and IL-10 (p < 0.001 and p < 0.05, respectively), key cytokines used by Treg cells to exert their immunosuppressive functions. Our findings suggest the contribution of both TGF-β and IL-10 in the suppressive activity of Treg cells.
    Journal
    |
    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    Hiltonol (poly-ICLC)
    3ms
    Mel 70: FUSA With Intratumoral PolyICLC in Regionally Advanced Resectable Melanoma (clinicaltrials.gov)
    P1, N=11, Recruiting, University of Virginia | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Hiltonol (poly-ICLC)
    3ms
    HAITEN-ICI: Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC (clinicaltrials.gov)
    P1/2, N=0, Withdrawn, VA Office of Research and Development | N=16 --> 0 | Trial completion date: Apr 2028 --> Jun 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jun 2026 --> Jun 2024
    Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date • Checkpoint inhibition • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Hiltonol (poly-ICLC)
    4ms
    Pirarubicin combined with TLR3 or TLR4 agonists enhances anti-tumor efficiency. (PubMed, Int Immunopharmacol)
    Our results provide new ideas for the combination strategy of THP with TLR agonists which improves prognosis of breast cancer.
    Journal • IO biomarker
    |
    TLR4 (Toll Like Receptor 4) • TLR3 (Toll Like Receptor 3)
    |
    Pinorubin (pirarubicin)
    4ms
    Dendritic Cell Vaccine for Patients With Brain Tumors (clinicaltrials.gov)
    P2, N=24, Completed, Jonsson Comprehensive Cancer Center | Active, not recruiting --> Completed | N=60 --> 24 | Trial completion date: Jan 2026 --> Aug 2024 | Trial primary completion date: Jan 2025 --> Aug 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    Hiltonol (poly-ICLC)
    5ms
    Mutant KRAS -Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer (clinicaltrials.gov)
    P1, N=37, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=25 --> 37
    Enrollment change
    |
    KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IFNG (Interferon, gamma) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule) • EPCAM (Epithelial cell adhesion molecule) • PMS1 (PMS1 protein homolog 1)
    |
    Hiltonol (poly-ICLC)
    5ms
    Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov)
    P2, N=24, Recruiting, Roswell Park Cancer Institute | Trial completion date: Aug 2025 --> Nov 2025 | Trial primary completion date: Aug 2025 --> Nov 2025
    Trial completion date • Trial primary completion date • Combination therapy • IO biomarker
    |
    CD8 (cluster of differentiation 8)
    |
    Intron A (interferon α-2b) • Ampligen (rintatolimod) • aDC1 vaccine • celecoxib oral
    5ms
    Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease (clinicaltrials.gov)
    P1, N=16, Not yet recruiting, Washington University School of Medicine
    New P1 trial
    |
    Opdivo (nivolumab) • Hiltonol (poly-ICLC)
    5ms
    Ampligen Compared to No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P2, N=90, Recruiting, AIM ImmunoTech Inc. | Trial completion date: Jul 2027 --> Apr 2028 | Trial primary completion date: Jun 2027 --> Mar 2028
    Trial completion date • Trial primary completion date • Metastases
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • Ampligen (rintatolimod)
    5ms
    Therapeutic Anti-Tumor Efficacy of DC-Based Vaccines Targeting TME-Associated Antigens Is Improved When Combined with a Chemokine-Modulating Regimen and/or Anti-PD-L1. (PubMed, Vaccines (Basel))
    We also evaluated whether combination vaccines incorporating anti-PD-L1 checkpoint blockade and/or a chemokine-modulating (CKM; IFNα + TLR3-L [rintatolimod] + Celecoxib) regimen would improve T cell infiltration/functionality in tumors yielding enhanced treatment benefits. Peptide-based vaccines that selectively target either melanoma antigens or TBVAs elicited a CD8+ T cell repertoire recognizing both tumor cells and tumor-associated VECs and pericytes in vitro, consistent with a treatment-induced epitope spreading mechanism. Notably, combination vaccines including anti-PD-L1 + CKM yielded superior therapeutic effects on tumor growth and animal survival, in association with the potentiation of polyfunctional CD8+ T cell reactivity against both tumor cells and tumor-associated vascular cells and a pro-inflammatory TME.
    Journal
    |
    CD8 (cluster of differentiation 8) • TLR3 (Toll Like Receptor 3) • IFNA1 (Interferon Alpha 1)
    |
    Ampligen (rintatolimod) • celecoxib oral
    5ms
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma) (clinicaltrials.gov)
    P1/2, N=22, Completed, Craig L Slingluff, Jr | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
    |
    CDX-1140 • Hiltonol (poly-ICLC)
    6ms
    NCI-2019-01192: Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery (clinicaltrials.gov)
    P2, N=30, Suspended, Roswell Park Cancer Institute | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026
    Trial completion date • Trial primary completion date • Surgery
    |
    Intron A (interferon α-2b) • Ampligen (rintatolimod) • aspirin
    6ms
    Mel 70: FUSA With Intratumoral PolyICLC in Regionally Advanced Resectable Melanoma (clinicaltrials.gov)
    P1, N=11, Not yet recruiting, University of Virginia
    New P1 trial • Metastases
    |
    Hiltonol (poly-ICLC)
    6ms
    A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov)
    P1, N=14, Terminated, Nicholas Butowski | Active, not recruiting --> Terminated; Industry sponsor decision
    Trial termination
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
    6ms
    Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery (clinicaltrials.gov)
    P1, N=30, Recruiting, Washington University School of Medicine | Active, not recruiting --> Recruiting
    Enrollment open • Surgery
    |
    Hiltonol (poly-ICLC)
    7ms
    GCC-16047: Pembrolizumab + Poly-ICLC in MRP Colon Cancer (clinicaltrials.gov)
    P1/2, N=42, Completed, Asha Nayak | N=31 --> 42
    Enrollment change • Mismatch repair • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • Hiltonol (poly-ICLC)
    7ms
    Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=45, Recruiting, Robert Edwards | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date • Checkpoint inhibition • Checkpoint block
    |
    CD4 (CD4 Molecule)
    |
    Keytruda (pembrolizumab) • cisplatin • Ampligen (rintatolimod)
    7ms
    SPOTLIGHT204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov)
    P2, N=60, Recruiting, Highlight Therapeutics | Not yet recruiting --> Recruiting
    Enrollment open
    |
    polyinosinic:polycytidylic acid (BO-112)
    7ms
    Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov)
    P2, N=24, Recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2025 --> Aug 2025
    Trial completion date • Combination therapy • IO biomarker
    |
    CD8 (cluster of differentiation 8)
    |
    Intron A (interferon α-2b) • Ampligen (rintatolimod) • aDC1 vaccine • celecoxib oral
    7ms
    A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma (clinicaltrials.gov)
    P1, N=6, Not yet recruiting, Jonsson Comprehensive Cancer Center | Initiation date: May 2024 --> Dec 2024
    Trial initiation date
    |
    Hiltonol (poly-ICLC)
    7ms
    Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=12, Recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2025 --> Jun 2025 | Trial primary completion date: Dec 2025 --> Jun 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    Keytruda (pembrolizumab) • Ampligen (rintatolimod) • Bioferon (interferon alpha 2b) • celecoxib oral
    7ms
    SPOTLIGHT204: Clinical Trial to Evaluate Safety, Tolerability and Preliminary Efficacy of BO-112 in Patients With BCC (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, Highlight Therapeutics
    New P2 trial
    |
    polyinosinic:polycytidylic acid (BO-112)
    8ms
    TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial. (PubMed, Nat Commun)
    Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.
    Clinical • P2 data • Clinical Trial,Phase II • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD38 (CD38 Molecule) • CD4 (CD4 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    |
    PD-1 expression • CD8 expression • ENTPD1 expression
    |
    Hiltonol (poly-ICLC)
    8ms
    HAITEN-ICI: Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC (clinicaltrials.gov)
    P1/2, N=16, Not yet recruiting, VA Office of Research and Development | Trial primary completion date: Mar 2026 --> Jun 2026
    Trial primary completion date • Checkpoint inhibition • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Hiltonol (poly-ICLC)
    8ms
    Dendritic Cell Vaccine for Patients With Brain Tumors (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date
    |
    Hiltonol (poly-ICLC)
    8ms
    Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C. (PubMed, J Immunother Cancer)
    Intratumoral injection of poly(I:C) sensitizes MHClow tumors to the antitumor effects of artLCMV-E7E6, resulting in a potent therapeutic synergy.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CCL3 (C-C Motif Chemokine Ligand 3) • IFNA1 (Interferon Alpha 1) • BATF3 (Basic Leucine Zipper ATF-Like Transcription Factor 3)
    |
    polyinosinic:polycytidylic acid (BO-112)
    9ms
    A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma (clinicaltrials.gov)
    P1, N=6, Not yet recruiting, Jonsson Comprehensive Cancer Center
    New P1 trial
    |
    Hiltonol (poly-ICLC)
    9ms
    Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery (clinicaltrials.gov)
    P1, N=25, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting
    Enrollment closed • Surgery
    |
    Hiltonol (poly-ICLC)
    9ms
    Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses. (PubMed, Clin Cancer Res)
    This study presents compelling evidence of the immune-stimulatory properties linked to TLR-3 activation through rintatolimod. Rintatolimod may break immunological tolerance by enhancing anti-tumor immunity through DC-mediated Th-cell responses. Furthermore, our findings lay the groundwork for investigating the potential synergy between TLR-3 activation and immune checkpoint inhibitor therapy to improve therapeutic outcomes.
    Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • PD-L2 (Programmed Cell Death 1 Ligand 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule) • BTLA (B And T Lymphocyte Associated) • TLR3 (Toll Like Receptor 3)
    |
    PD-L2 expression
    |
    Ampligen (rintatolimod)
    10ms
    NF111: A Phase II Trial of Poly-ICLC for Low-Grade Gliomas (clinicaltrials.gov)
    P2, N=20, Recruiting, University of Alabama at Birmingham | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2025 --> Feb 2026
    Trial completion date • Trial primary completion date
    |
    NF1 (Neurofibromin 1)
    |
    NF1 mutation
    |
    Hiltonol (poly-ICLC)
    10ms
    Safety and Immunogenicity of Personalized Genomic Vaccine and Tumor Treating Fields (TTFields) to Treat Glioblastoma (clinicaltrials.gov)
    P1, N=13, Active, not recruiting, Albert Einstein College of Medicine | Trial completion date: May 2024 --> May 2025
    Trial completion date
    |
    Hiltonol (poly-ICLC)
    10ms
    Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ (clinicaltrials.gov)
    P1, N=50, Recruiting, Finn, Olivera, PhD | Not yet recruiting --> Recruiting | Trial completion date: Jul 2027 --> Aug 2028
    Enrollment open • Trial completion date
    |
    MUC1 (Mucin 1)
    |
    letrozole • anastrozole • exemestane • Hiltonol (poly-ICLC)
    10ms
    NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date • Surgery
    |
    Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)