^
    17d
    Pembrolizumab +/- SD-101 in Hormone-Naïve Oligometastatic Prostate Cancer With RT and iADT (clinicaltrials.gov)
    P2, N=23, Active, not recruiting, David Oh | Trial completion date: Oct 2024 --> Aug 2025 | Trial primary completion date: Oct 2024 --> Aug 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Keytruda (pembrolizumab) • abiraterone acetate • prednisone • leuprolide acetate for depot suspension • nelitolimod (SD-101)
    20d
    Local CpG-Stat3 siRNA treatment improves antitumor effects of immune checkpoint inhibitors. (PubMed, Mol Ther Nucleic Acids)
    Furthermore, locally delivered CpG-Stat3 siRNA enhanced CD8+ T cell tumor infiltration and antitumor activity in a xenograft tumor model. Overall, our studies in both B cell lymphoma and melanoma mouse models demonstrate the potential of combinatory immunotherapy with CpG-Stat3 siRNA and checkpoint inhibitors as a therapeutic strategy for B cell lymphoma and melanoma.
    Journal • Checkpoint inhibition
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3) • TLR9 (Toll Like Receptor 9)
    |
    DUET-201
    24d
    Cryoablation and Arterial Infusion of SD-101 in Combination With Durvalumab and Tremelimumab (clinicaltrials.gov)
    P1, N=20, Not yet recruiting, University of California, San Diego
    New P1 trial • Combination therapy • Metastases
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl) • nelitolimod (SD-101)
    24d
    Invention and characterization of a systemically administered, attenuated and killed bacteria-based multiple immune receptor agonist for anti-tumor immunotherapy. (PubMed, Front Immunol)
    Decoy10 and a closely related product, Decoy20, produced single agent anti-tumor activity or combination-mediated durable regression of established subcutaneous, metastatic or orthotopic colorectal, hepatocellular (HCC), pancreatic, and non-Hodgkin's lymphoma (NHL) tumors in mice, with induction of both innate and adaptive immunological memory (syngeneic and human tumor xenograft models). Decoy bacteria combination-mediated regressions were observed with a low-dose, oral non-steroidal anti-inflammatory drug (NSAID), anti-PD-1 checkpoint therapy, low-dose cyclophosphamide (LDC), and/or a targeted antibody (rituximab). Efficient tumor eradication was associated with plasma expression of 15-23 cytokines and chemokines, broad induction of cytokine, chemokine, innate and adaptive immune pathway genes in tumors, cold to hot tumor inflammation signature transition, and required NK, CD4+ and CD8+ T cells, collectively demonstrating a role for both innate and adaptive immune activation in the anti-tumor immune response.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • STING (stimulator of interferon response cGAMP interactor 1) • TLR4 (Toll Like Receptor 4) • TLR2 (Toll Like Receptor 2)
    |
    Rituxan (rituximab) • cyclophosphamide
    1m
    CMP-001 for Relapsed and Refractory Lymphoma (clinicaltrials.gov)
    P1/2, N=39, Active, not recruiting, Umar Farooq | Trial primary completion date: Apr 2025 --> Aug 2024
    Trial primary completion date
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    1m
    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 2024 --> Dec 2028 | Trial primary completion date: Jul 2024 --> Dec 2028
    Trial completion date • Trial primary completion date
    1m
    CMP-001 for Relapsed and Refractory Lymphoma (clinicaltrials.gov)
    P1/2, N=39, Active, not recruiting, Umar Farooq | Suspended --> Active, not recruiting
    Enrollment closed
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    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=77, Terminated, Regeneron Pharmaceuticals | Active, not recruiting --> Terminated; Sponsor Decision related to study drug supply
    Trial termination • Combination therapy • Metastases
    |
    Libtayo (cemiplimab-rwlc) • 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) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    BRAF (B-raf proto-oncogene)
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    2ms
    Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial. (PubMed, Cancer Cell)
    Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov identifier: NCT03618641.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8)
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    2ms
    A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Cavrotolimod in Subjects with Chronic Hepatitis B Infection (ACTRN12624000808549)
    P1, N=40, Recruiting, Bluejay Therapeutics, Inc | Not yet recruiting --> Recruiting
    Enrollment open • Trial initiation date
    |
    cavrotolimod (AST-008)
    2ms
    PUL-042 Treatment in Patients with Parainfluenza Virus (PIV), Human Metapneumovirus (hMPV) or Respiratory Syncytial Virus (RSV) (clinicaltrials.gov)
    P2, N=100, Not yet recruiting, Pulmotect, Inc.
    New P2 trial
    2ms
    CMP-001 in Combination With Nivolumab in Subjects With Advanced Melanoma (clinicaltrials.gov)
    P2, N=44, Terminated, Regeneron Pharmaceuticals | Completed --> Terminated; Business Decision
    Trial termination • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    2ms
    CMP-001-011: CMP-001 in Combination With Nivolumab Compared to Nivolumab Monotherapy in Subjects With Advanced Melanoma (clinicaltrials.gov)
    P2/3, N=20, Terminated, Regeneron Pharmaceuticals | Completed --> Terminated; Business Decision
    Trial termination • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    2ms
    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, Terminated, Regeneron Pharmaceuticals | Completed --> Terminated; Business Decision
    Trial termination • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • vidutolimod (CMP-001)
    2ms
    Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination with Nivolumab Vs. Nivolumab (clinicaltrials.gov)
    P2, N=9, Completed, Diwakar Davar | Active, not recruiting --> Completed | Trial completion date: Jul 2028 --> Aug 2024 | Trial primary completion date: Jul 2028 --> Aug 2024
    Trial completion • Trial completion date • Trial primary completion date • Combination therapy
    |
    CD8 (cluster of differentiation 8)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • vidutolimod (CMP-001)
    2ms
    PRIMO: Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers (clinicaltrials.gov)
    P1, N=25, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=72 --> 25 | Active, not recruiting --> Terminated; The part A of the trial has been completed according to the protocol. The part B has not been opened because of unfeasibility (experimental products not yet available).
    Enrollment change • Trial termination • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • tilsotolimod (IMO-2125)
    3ms
    Regional lymph node changes on breast MRI in patients with early-stage breast cancer receiving neoadjuvant chemo-immunotherapy. (PubMed, Breast Cancer Res Treat)
    The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Keytruda (pembrolizumab) • paclitaxel • nelitolimod (SD-101)
    4ms
    ABESt: Anthrax AV7909 Boost Evaluation Study (clinicaltrials.gov)
    P2, N=220, Active, not recruiting, Biomedical Advanced Research and Development Authority | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2024 --> Aug 2025
    Enrollment closed • Trial primary completion date
    4ms
    INCLINE-101: A Dose Escalation and Expansion Study of TAC-001 in Patients With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=72, Active, not recruiting, Tallac Therapeutics | Recruiting --> Active, not recruiting | N=200 --> 72
    Enrollment closed • Enrollment change • Metastases
    |
    mozistobart zoratolimod (TAC-001)
    4ms
    CMP-001-011: CMP-001 in Combination With Nivolumab Compared to Nivolumab Monotherapy in Subjects With Advanced Melanoma (clinicaltrials.gov)
    P2/3, N=20, Completed, Regeneron Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    4ms
    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=77, Active, not recruiting, Regeneron Pharmaceuticals | Suspended --> Active, not recruiting | N=225 --> 77 | Trial completion date: Jul 2027 --> Oct 2024 | Trial primary completion date: Jul 2027 --> Oct 2024
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Libtayo (cemiplimab-rwlc) • vidutolimod (CMP-001)
    4ms
    Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas. (PubMed, JCI Insight)
    Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.
    Preclinical • Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • GZMB (Granzyme B)
    4ms
    B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B (clinicaltrials.gov)
    P3, N=640, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting --> Completed
    Trial completion
    |
    CD4 (CD4 Molecule)
    5ms
    Vidutolimod (CMP-001) in Combination With Nivolumab for the Treatment of Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P2, N=10, Suspended, Emory University | Recruiting --> Suspended
    Trial suspension • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • vidutolimod (CMP-001)
    5ms
    HEPLISAV-B® in Adults With End-Stage Renal Disease (ESRD) Undergoing Hemodialysis (clinicaltrials.gov)
    P1, N=119, Completed, Dynavax Technologies Corporation | Active, not recruiting --> Completed
    Trial completion
    5ms
    Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases. (PubMed, J Immunother Cancer)
    The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
    Journal • Checkpoint inhibition
    |
    PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M) • ITGAX (Integrin Subunit Alpha X)
    |
    nelitolimod (SD-101)
    6ms
    Combinatorial Therapy to Induce an HIV Remission (clinicaltrials.gov)
    P1/2, N=11, Active, not recruiting, University of California, San Francisco | Trial completion date: Dec 2024 --> Dec 2025
    Trial completion date
    |
    CD4 (CD4 Molecule)
    7ms
    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, Completed, Diwakar Davar | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Mar 2024 | Trial primary completion date: Dec 2024 --> Feb 2024
    Trial completion • 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)
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    7ms
    An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer. (PubMed, Cancer Control)
    CpG ODN and trastuzumab treatment of metastatic HER2 + breast cancer was safe but was not tolerable for all patients. This combination did induce potentially predictive immune profile changes in treated patients with metastatic HER2 + breast cancer, the significance of which needs to be further explored.
    Clinical Trial,Phase II • Journal • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-1 (Programmed cell death 1) • VEGFD (Vascular Endothelial Growth Factor D)
    |
    Herceptin (trastuzumab) • Herceptin Hylecta (trastuzumab/hyaluronidase-oysk) • Promune (agatolimod)
    7ms
    Trial of the Immunogenicity, Safety, and Tolerability of rF1V Vaccine With CpG 1018® Adjuvant Compared With rF1V Vaccine in Adults 18 to 55 Years of Age (clinicaltrials.gov)
    P2, N=200, Completed, Dynavax Technologies Corporation | Active, not recruiting --> Completed
    Trial completion
    8ms
    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)
    8ms
    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
    9ms
    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)
    9ms
    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)
    9ms
    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)
    9ms
    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
    10ms
    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
    10ms
    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)
    10ms
    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)
    10ms
    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)
    10ms
    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