^
    15d
    Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination With Nivolumab vs. Nivolumab (clinicaltrials.gov)
    P2, N=9, Active, not recruiting, Diwakar Davar | Suspended --> Active, not recruiting | N=36 --> 9 | Trial completion date: Jul 2030 --> Jul 2028
    Enrollment closed • Enrollment change • Trial completion date • Combination therapy
    |
    CD8 (cluster of differentiation 8)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • vidutolimod (CMP-001)
    1m
    Anthrax AV7909 Liquid vs Lyophilized (clinicaltrials.gov)
    P1, N=41, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Nov 2023
    Trial completion date • Trial primary completion date
    1m
    A Trial To Find Out If Vidutolimod Together With Cemiplimab Is Safe And If It Works In Adult Participants With Advanced Cancer Or Metastatic Cancer (clinicaltrials.gov)
    P2, N=225, Suspended, Regeneron Pharmaceuticals | Recruiting --> Suspended
    Trial suspension • Combination therapy • Metastases
    |
    Libtayo (cemiplimab-rwlc) • vidutolimod (CMP-001)
    2ms
    CMP-001 for Relapsed and Refractory Lymphoma (clinicaltrials.gov)
    P1/2, N=39, Suspended, Umar Farooq | Recruiting --> Suspended
    Trial suspension
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    2ms
    A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy in Patients With Operable Melanoma (clinicaltrials.gov)
    P2, N=60, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Combination therapy
    |
    BRAF (B-raf proto-oncogene)
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    2ms
    Comparison Between 2-dose Versus 3-dose Regimens of Heplisav B in Cirrhosis (clinicaltrials.gov)
    P4, N=200, Recruiting, Mercy Medical Center | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024
    Trial completion date • Trial primary completion date
    2ms
    Innate Immunity Stimulation Via TLR9 in Early AD (clinicaltrials.gov)
    P1, N=15, Recruiting, NYU Langone Health | N=39 --> 15 | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
    Enrollment change • Trial completion date • Trial primary completion date
    3ms
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2, N=14, Active, not recruiting, Diwakar Davar | Trial completion date: Sep 2027 --> Aug 2025 | Trial primary completion date: Sep 2025 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Pan tumor • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RAS wild-type
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    3ms
    CMP-001 in Combination With Nivolumab in Subjects With Advanced Melanoma (clinicaltrials.gov)
    P2, N=44, Completed, Regeneron Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    3ms
    Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant (clinicaltrials.gov)
    P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed
    Trial completion
    |
    HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
    |
    Promune (agatolimod)
    3ms
    Ph2 NK Cell Enriched DCIs w/wo RLR9 Agonist, DUK-CPG-001 From Donors Following Allogeneic SCT (clinicaltrials.gov)
    P2, N=36, Active, not recruiting, Cristina Gasparetto | N=100 --> 36
    Enrollment change
    3ms
    Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination With Nivolumab vs. Nivolumab (clinicaltrials.gov)
    P2, N=36, Suspended, Diwakar Davar | Recruiting --> Suspended
    Trial suspension • Combination therapy
    |
    CD8 (cluster of differentiation 8)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • vidutolimod (CMP-001)
    3ms
    A Trial To Find Out If Vidutolimod Together With Cemiplimab Is Safe And If It Works In Adult Participants With Advanced Cancer Or Metastatic Cancer (clinicaltrials.gov)
    P2, N=225, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Mar 2027 --> Jul 2027 | Trial primary completion date: Mar 2027 --> Jul 2027
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Libtayo (cemiplimab-rwlc) • vidutolimod (CMP-001)
    3ms
    CMP-001 in Combination With Nivolumab in Subjects With Advanced Melanoma (clinicaltrials.gov)
    P2, N=44, Active, not recruiting, Regeneron Pharmaceuticals | Trial completion date: Oct 2024 --> Feb 2024 | Trial primary completion date: Oct 2024 --> Feb 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    3ms
    Anthrax AV7909 Liquid vs Lyophilized (clinicaltrials.gov)
    P1, N=41, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Mar 2023 | Trial primary completion date: Nov 2023 --> Mar 2023
    Trial completion • Trial completion date • Trial primary completion date
    3ms
    A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov)
    P1, N=24, Recruiting, Universitätsklinikum Hamburg-Eppendorf | Not yet recruiting --> Recruiting
    Enrollment open
    3ms
    Antitumoral effect of local injection of TLR-9 agonist emulsified in Lipiodol with systemic anti-PD-1 in a murine model of colorectal carcinoma. (PubMed, Front Immunol)
    Lipiodol, apart from its radiopaque properties, is an efficient drug-delivery system. The formulated oil-in-water emulsion allows efficient loading and control release of CpG, which induces favorable immune modifications in this murine tumor model.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma)
    |
    IFNG expression
    4ms
    CMP-001-007: CMP-001 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P2, N=24, Completed, Regeneron Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    4ms
    Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy. (PubMed, Front Immunol)
    To better understand immune alterations associated with ICB resistance, we assessed blood biomarkers in renal cancer patients classified as responders or non-responders to first line nivolumab/ipilimumab immunotherapy...To assess whether STAT3 inhibition within these cell subsets can promote antitumor immune responses and/or enhance sensitivity to ICB in vivo, we used an original antisense oligonucleotide (ASO) strategy for myeloid-cell selective STAT3 knockdown (CpG-STAT3ASO)...Therapeutic efficacy correlated with activation of dendritic cells (DCs) and M1 macrophages in the tumor microenvironment, reduced percentages of regulatory T cells (Tregs) and the expansion of CD8 T cells in both tumor models. Our study underscores the potential of using myeloid-cell targeted CpG-STAT3 inhibitors for genitourinary cancer therapy to disrupt tolerogenic signaling, restore immune cell activity and sensitivity to immune checkpoint inhibitors and/or T cell-based immunotherapies.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IL10 (Interleukin 10) • IL1R1 (Interleukin 1 receptor, type I)
    |
    CXCL8 elevation
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • DUET-101
    4ms
    Haystack Oncology, developer of Haystack MRD, and TriSalus Life Sciences collaborate in connection with the clinical development of TriSalus’ TLR9 agonist in hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and pancreatic adenocarcinoma (PRNewswire)
    "Haystack Oncology...has entered a research collaboration with TriSalus Life Sciences to evaluate therapeutic response and provide molecular insights in connection with the clinical development of TriSalus' SD-101, an investigational class C toll-like receptor-9 (TLR9) agonist. SD-101 is delivered via hepatic arterial infusion or pancreatic retrograde venous infusion in their phase 1 and 1b clinical trials using their proprietary Pressure-Enabled Drug Delivery™ (PEDD™) to overcome the challenges associated with intratumoral pressure for patients diagnosed with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and pancreatic adenocarcinoma."
    Licensing / partnership
    |
    nelitolimod (SD-101)
    4ms
    Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. (PubMed, Nat Med)
    Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017 .
    P1 data • Journal • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    KRAS mutation • KRAS G12D • KRAS G12
    |
    ELI-002 7P • Promune (agatolimod)
    5ms
    CONCLUDE: The Efficacy and Safety of Cobitolimod in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis (clinicaltrials.gov)
    P3, N=171, Terminated, InDex Pharmaceuticals | N=440 --> 171 | Trial completion date: Dec 2024 --> Dec 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Dec 2023; Due to futility
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    5ms
    TS-PERIO-02: Pressure Enabled Delivery of SD-101 With Checkpoint Blockade for Primary Liver Tumors (clinicaltrials.gov)
    P1/2, N=89, Active, not recruiting, TriSalus Life Sciences, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2
    Enrollment closed • Phase classification • Checkpoint inhibition • Checkpoint block • Immuno-oncology
    |
    FGFR2 (Fibroblast growth factor receptor 2)
    |
    FGFR2 mutation
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • nelitolimod (SD-101)
    5ms
    TS-PERIO-01: Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma (clinicaltrials.gov)
    P1, N=80, Active, not recruiting, TriSalus Life Sciences, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Checkpoint inhibition • Checkpoint block • Metastases • Immuno-oncology
    |
    Yervoy (ipilimumab) • Opdualag (nivolumab/relatlimab) • nelitolimod (SD-101) • relatlimab (BMS-986016)
    5ms
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2, N=14, Active, not recruiting, Diwakar Davar | Recruiting --> Active, not recruiting | Phase classification: P2a --> P2 | N=61 --> 14 | Trial completion date: Dec 2029 --> Sep 2027 | Trial primary completion date: Nov 2026 --> Sep 2025
    Enrollment closed • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Pan tumor • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RAS wild-type
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    5ms
    A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Universitätsklinikum Hamburg-Eppendorf | Phase classification: P1a --> P1 | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Jun 2024 --> Feb 2025
    Phase classification • Trial completion date • Trial primary completion date
    5ms
    The PERIO-03 Trial: Technical Feasibility and Safety of a Novel Pancreatic Retrograde Venous Immunotherapy Infusion Intervention for Locally Advanced Pancreatic Ductal Adenocarcinoma (SIR 2024)
    Materials and The PERIO-03 trial utilizes a uniquely designed occlusive catheter (TriSalus Infusion System (TIS), TriSalus Life Sciences) for the delivery of the immunotherapeutic agent, SD-101, via Pancreatic Retrograde Venous Infusion (PRVI)... Current experience with the novel transvenous immunotherapy delivery intervention in the PERIO-03 study indicates that this PRVI procedure is technically feasible and safe.
    Clinical • Metastases
    |
    nelitolimod (SD-101)
    5ms
    ABESt: Anthrax AV7909 Boost Evaluation Study (clinicaltrials.gov)
    P2, N=220, Recruiting, Biomedical Advanced Research and Development Authority | Not yet recruiting --> Recruiting
    Enrollment open
    6ms
    Toll-like Receptor-9 Agonist Reverses T Cell Exhaustion in a Murine Model of Pediatric B-ALL (ASH 2023)
    Overall, this study reveals that the functional impact of interactions between B-ALL cells and the immune system evolves during leukemia development. These insights could inform therapeutic strategies to overcome B-ALL immune evasion mechanisms and enhance patient outcomes.
    Preclinical • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD4 (CD4 Molecule) • TLR9 (Toll Like Receptor 9)
    |
    PD-1 expression • HAVCR2 expression • CTLA4 expression
    6ms
    Immunogenicity of rabies virus G mRNA formulated with lipid nanoparticles and nucleic acid immunostimulators in mice. (PubMed, Vaccine)
    In addition, in the pre- and post-exposure challenge assays, LNP + CPG 1018 capsulated RABV G mRNA induced 100 % protection against 25 LD50 of RABV infection with highest inhibition efficacy of viral replication with the decreased virus genome detected by qRT-PCR. These results showed that RABV G mRNA capsulated with LNP immune-stimulating nucleic acids CPG 1018 showed promise as a safe and economical rabies vaccine candidate.
    Preclinical • Journal
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule)
    6ms
    TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, Ronald Levy | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    nelitolimod (SD-101) • BMS-986178
    6ms
    TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma (clinicaltrials.gov)
    P1/2, N=21, Completed, Robert Lowsky | Active, not recruiting --> Completed | N=30 --> 21 | Trial completion date: Nov 2023 --> May 2023 | Trial primary completion date: Nov 2023 --> May 2023
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    Imbruvica (ibrutinib) • nelitolimod (SD-101)
    6ms
    CpG-STAT3 siRNA CAS3/SS3 and Localized Radiation Therapy for the Treatment of Relapsed/Refractory B-Cell NHL (clinicaltrials.gov)
    P1, N=0, Withdrawn, City of Hope Medical Center | N=18 --> 0 | Trial completion date: Dec 2024 --> Jan 2024 | Recruiting --> Withdrawn | Trial primary completion date: Dec 2024 --> Jan 2024
    Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date • Combination therapy
    |
    DUET-201
    6ms
    Anthrax AV7909 Liquid vs Lyophilized (clinicaltrials.gov)
    P1, N=41, Active, not recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Mar 2023 --> Nov 2023
    Trial primary completion date
    6ms
    CMP-001-007: CMP-001 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P2, N=24, Active, not recruiting, Regeneron Pharmaceuticals | Trial completion date: Jul 2024 --> Jan 2024 | Trial primary completion date: Jul 2024 --> Jan 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    7ms
    Loss of the OX40 Target in Lymphoma Patients after Combining an Anti-OX40 Agonist Antibody with in Situ Vaccination (ASH 2023)
    STUDY: Fourteen patients with low-grade lymphoma received low-dose (2Gy x 2) radiotherapy to a single tumor site followed by 5 weekly intratumoral injections of 2 mg CpG-ODN (SD-101, TriSalus Life Sciences) and 3.75 mg anti-OX40 antibody into the same site...This loss was reproduced by in vitro assays where activated blood CD4 T cells exhibited a loss of cell surface OX40 when cultured with BMS-986178... Our observations suggest that treatment with an agonistic anti-OX40 antibody induced a loss of OX40 on the cell surface of effector CD4 T cells in the tumor microenvironment. Fewer molecules of OX40 receptor may have constrained the efficacy of subsequent anti-OX40 infusions and may explain why the clinical responses observed in this study were lower than observed in our past clinical trials of in situ vaccination.
    Clinical
    |
    CD4 (CD4 Molecule)
    |
    nelitolimod (SD-101) • BMS-986178
    7ms
    ABESt: Anthrax AV7909 Boost Evaluation Study (clinicaltrials.gov)
    P2, N=220, Not yet recruiting, Biomedical Advanced Research and Development Authority | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Jul 2024
    Trial completion date • Trial primary completion date
    7ms
    Immunotherapy with STING and TLR9 agonists promotes synergistic therapeutic efficacy with suppressed cancer-associated fibroblasts in colon carcinoma. (PubMed, Front Immunol)
    In this study, we investigated the immunotherapeutic effects of ADU-S100 as a STING agonist and CpG ODN1826 as a TLR9 agonist in a preclinical model of colon carcinoma. Remarkably, the significant downregulation of CAFs in the TME indicated that suppression of tumorigenesis occurred after immunoadjuvant therapy. The results illustrate the potential of targeting the STING and TLR9 pathways as powerful immunoadjuvants in the treatment of preclinical colon carcinoma and the possibility of harnessing these pathways in future therapeutic approaches.
    Journal • IO biomarker
    |
    STING (stimulator of interferon response cGAMP interactor 1)
    |
    ADU-S100
    7ms
    Anthrax AV7909 Liquid vs Lyophilized (clinicaltrials.gov)
    P1, N=41, Active, not recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Sep 2023 --> Mar 2023
    Trial completion date • Trial primary completion date
    7ms
    Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=28, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    Yervoy (ipilimumab) • lefitolimod (MGN1703)
    8ms
    TS-PERIO-02: Pressure Enabled Delivery of SD-101 With Checkpoint Blockade for Primary Liver Tumors (clinicaltrials.gov)
    P1b/2, N=89, Recruiting, TriSalus Life Sciences, Inc. | Trial primary completion date: Aug 2023 --> Dec 2023
    Trial primary completion date • Checkpoint inhibition • Checkpoint block • Immuno-oncology
    |
    FGFR2 (Fibroblast growth factor receptor 2)
    |
    FGFR2 mutation
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • nelitolimod (SD-101)