- |||||||||| motolimod (VTX 2337) / BMS
Journal: TLR8 agonist Motolimod-induced inflammatory death for treatment of acute myeloid leukemia. (Pubmed Central) - May 29, 2023
In terms of mechanism, cellular experiments in AML cell lines proved that TLR8 and LKB1/AMPK are the key distinct mechanisms for MTL triggered caspase-3-dependent cell death and the expression of a large number of inflammatory factors. In conclusion, our findings identified the immunoactivator MTL as a single agent exerting significant anti-AML activity in vitro and in vivo, with strong potential for clinical translation.
- |||||||||| motolimod (VTX 2337) / BMS
Journal: Identification of new potent agonists for toll-like receptor 8 by virtual screening methods, molecular dynamics simulation, and MM-GBSA. (Pubmed Central) - Dec 6, 2022
Previous studies have shown that TLR8 agonists e.g. Motolimod can be used to treat patients with last-stage cancer...As the RMSD results showed that compound A has very good flexibility, in terms of energy calculated using the MM-GBSA method, complex B and TLR8 showed the lowest energy level compared to the rest of the complexes. These observations suggest that these two compounds could be used as TLR8 agonists with the desired pharmacological features in future experimental studies.Communicated by Ramaswamy H. Sarma.
- |||||||||| motolimod (VTX 2337) / BMS
Journal, IO biomarker: Ginsenoside Rh2 Ameliorates Neuropathic Pain by inhibition of the miRNA21-TLR8-MAPK axis. (Pubmed Central) - Aug 31, 2022
Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.
- |||||||||| Opdivo (nivolumab) / BMS, motolimod (VTX 2337) / BMS
Enrollment change, Trial termination, Combination therapy: PBI-CEL-01: Intratumoral Microdosing of Motolimod in HNSCC (clinicaltrials.gov) - Apr 14, 2022
P1, N=1, Terminated,
These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy. N=12 --> 1 | Recruiting --> Terminated; Partner Termination
- |||||||||| motolimod (VTX 2337) / BMS
Generation of humanized TLR8 mice for the evaluation of human TLR8 agonists (Section 12) - Mar 9, 2022 - Abstract #AACR2022AACR_4355;
TLR8 agonists (e.g. VTX-2337) are undergoing clinical trials as immune stimulants in combination therapy for some cancers...We observed TNFα secretion in B-hTLR8 mice but not in wild-type mice. Therefore, B-hTLR8 mouse model is a promising model for preclinical in vivo studies to evaluate TLR8 agonists and antibody-conjugated TLR8 agonists.
- |||||||||| Opdivo (nivolumab) / BMS, motolimod (VTX 2337) / BMS
Biomarker, Trial completion, Enrollment change, Trial completion date, Trial primary completion date, Combination therapy: A Study to Evaluate Immune Biomarker Modulation in Response to VTX-2337 in Combination With an Anti- PD-1 Inhibitor in Head and Neck Cancer (clinicaltrials.gov) - Feb 25, 2022
P1b, N=15, Completed,
Therefore, B-hTLR8 mouse model is a promising model for preclinical in vivo studies to evaluate TLR8 agonists and antibody-conjugated TLR8 agonists. Recruiting --> Completed | N=72 --> 15 | Trial completion date: Aug 2022 --> Jan 2022 | Trial primary completion date: May 2022 --> Jan 2022
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, motolimod (VTX 2337) / BMS
Journal, Combination therapy, IO biomarker: The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent. (Pubmed Central) - Sep 9, 2021
Depletion of CD4+ T cells, CD8+ T cells and NK cells were all able to abolish the anti-tumor effect of VTX-2337+ cetuximab. Altogether, VTX-2337 remains promising as an adjuvant for cetuximab-based therapy however patients with high TLR8 expression may be more likely to derive benefit from this drug combination compared to patients with low TLR8 expression.
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, motolimod (VTX 2337) / BMS
Trial completion: Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - Sep 5, 2021
P1/2, N=53, Completed,
Altogether, VTX-2337 remains promising as an adjuvant for cetuximab-based therapy however patients with high TLR8 expression may be more likely to derive benefit from this drug combination compared to patients with low TLR8 expression. Active, not recruiting --> Completed
- |||||||||| Opdivo (nivolumab) / BMS, motolimod (VTX 2337) / BMS
Trial completion date, Trial primary completion date, Combination therapy: PBI-CEL-01: Intratumoral Microdosing of Motolimod in HNSCC (clinicaltrials.gov) - May 12, 2021
P1, N=12, Recruiting,
Targeting TLR8 signaling may be effective for the treatment of TNP. Trial completion date: Aug 2021 --> Mar 2022 | Trial primary completion date: Aug 2021 --> Dec 2021
- |||||||||| Zyclara (imiquimod) / Mochida, Mylan, Bausch Health, Promune (agatolimod) / Pfizer, motolimod (VTX 2337) / BMS
Review, Journal: Harnessing the immune system to fight cancer with Toll-like receptor and RIG-I-like receptor agonists. (Pubmed Central) - Mar 16, 2021
The phenomena of pattern-recognition receptor tolerance and reprogramming and their implications for immunotherapy are discussed. Finally, novel delivery systems that target the immune-stimulating drugs to the tumor or the tumor-draining lymph nodes to enhance their efficacy and safety are presented.
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, motolimod (VTX 2337) / BMS
Trial completion date: Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - Mar 10, 2021
P1/2, N=53, Active, not recruiting,
Finally, novel delivery systems that target the immune-stimulating drugs to the tumor or the tumor-draining lymph nodes to enhance their efficacy and safety are presented. Trial completion date: Jun 2020 --> Jun 2021
- |||||||||| Opdivo (nivolumab) / BMS, motolimod (VTX 2337) / BMS
Enrollment open, Combination therapy: PBI-CEL-01: Intratumoral Microdosing of Motolimod in HNSCC (clinicaltrials.gov) - Feb 12, 2021
P1, N=12, Recruiting,
Trial completion date: Jun 2020 --> Jun 2021 Not yet recruiting --> Recruiting
- |||||||||| Zyclara (imiquimod) / Mochida, Mylan, Bausch Health, Vesimune (imiquimod) / UroGen, motolimod (VTX 2337) / BMS
Review, Journal: Trial Watch: experimental TLR7/TLR8 agonists for oncological indications. (Pubmed Central) - Sep 18, 2020
In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents.
- |||||||||| fluorouracil / Generic mfg., Erbitux (cetuximab) / Eli Lilly, EMD Serono, Opdivo (nivolumab) / Ono Pharma, BMS
Journal: Current Prospects of Molecular Therapeutics in Head and Neck Squamous Cell Carcinoma. (Pubmed Central) - Jul 5, 2020
Currently, its major utility is in palliation of recurrent and/or metastatic HNSCC as a part of the EXTREME regimen alongside cisplatin/carboplatin and fluorouracil...Recent accelerated approval of two immune checkpoint receptor blockers, pembrolizumab and nivolumab, has rejuvenated enthusiasm among clinicians and researchers by opening up a new domain for targeted and co-targeted therapeutics...Immunotherapeutic agents belonging to different classes, such as durvalumab, epacadostat, motolimod, and T4 immunotherapy, are all being investigated presently in various therapeutic roles...Phase I/II trials are underway evaluating the safety profile, tolerable limits, and therapeutic efficacy of several therapeutic vaccines against HPV-driven HNSCC. Similarly, co-targeting therapeutics and precision medicine concepts are exploring newer and effective options including individuating the therapy based on particular tumor's molecular makeup and so on, the results of which are expected to change the landscape of HNSCC.
- |||||||||| Review, Journal: Therapeutic potential of toll-like receptors in treatment of gynecological cancers. (Pubmed Central) - Mar 5, 2020
Some TLR agonists that are of potential interest in the treatment of gynecological lesions include imiquimod, motolimod, cervarix, and CpG-oligodeoxynucleotides (ODNs). In this review, we outline the different functions of TLRs in gynecological cancer with particular emphasis on the value of TLR agonists as a potential therapeutic target in the treatment of gynecological cancer.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, motolimod (VTX 2337) / BMS
Biomarker, Clinical, Journal, IO biomarker: Effect of Adding Motolimod to Standard Combination Chemotherapy and Cetuximab Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial. (Pubmed Central) - Oct 11, 2019
P2
Combination treatment with platinum (carboplatin or cisplatin), fluorouracil, cetuximab (the EXTREME regimen), and either placebo or motolimod, each administered intravenously every 3 weeks...Significant benefit was observed in HPV-positive patients and those with injection site reactions, suggesting that TLR8 stimulation may benefit subset- and biomarker-selected patients. ClinicalTrials.gov identifier: NCT01836029.
- |||||||||| motolimod (VTX 2337) / Celgene
Preclinical, Journal, IO Biomarker: TLR8 and its endogenous ligand miR-21 contribute to neuropathic pain in murine DRG. (Pubmed Central) - Sep 6, 2019
Intrathecal injection of miR-21 showed the similar effects as VTX-2337 and inhibition of miR-21 in the DRG attenuated neuropathic pain. The present study reveals a previously unknown role of TLR8 in the maintenance of neuropathic pain, suggesting that miR-21-TLR8 signaling may be potential new targets for drug development against this type of chronic pain.
- |||||||||| motolimod (VTX 2337) / Celgene
Preclinical, Journal, Myeloid-derived suppressor cells, IO Biomarker: TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells. (Pubmed Central) - Apr 17, 2019
...We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function...There is increasing evidence that MDSCs contribute to the progression of cancer by inhibiting tumor-directed T cells. TLR8 agonists may synergize with cancer immunotherapeutic approaches to enhance the antitumor effects of the adaptive immune response.
- |||||||||| motolimod (VTX 2337) / BMS
Trial completion date, Trial termination, Immunomodulating, Metastases: TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors (clinicaltrials.gov) - Sep 5, 2018
P1, N=4, Terminated,
TLR8 agonists may synergize with cancer immunotherapeutic approaches to enhance the antitumor effects of the adaptive immune response. Trial completion date: Aug 2018 --> Jun 2017 | Completed --> Terminated; permanently closed per sponsor's request
- |||||||||| motolimod (VTX 2337) / BMS
Trial completion, Trial completion date, Trial primary completion date, Immunomodulating, Metastases: TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors (clinicaltrials.gov) - Sep 4, 2018
P1, N=4, Completed,
Trial completion date: Aug 2018 --> Jun 2017 | Completed --> Terminated; permanently closed per sponsor's request Active, not recruiting --> Completed | Trial completion date: May 2021 --> Aug 2018 | Trial primary completion date: May 2021 --> Sep 2016
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, motolimod (VTX 2337) / BMS
Trial completion date, Trial primary completion date: Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - Aug 7, 2018
P1/2, N=53, Active, not recruiting,
Active, not recruiting --> Completed | Trial completion date: May 2021 --> Aug 2018 | Trial primary completion date: May 2021 --> Sep 2016 Trial completion date: Dec 2018 --> Mar 2019 | Trial primary completion date: Jun 2018 --> Dec 2018
- |||||||||| motolimod (VTX 2337) / BMS
Journal: Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemo-immunotherapy. (Pubmed Central) - Jun 29, 2017
P1
Clinicaltrials.gov, NCT 01666444. These results are the first to demonstrate the value of pharmacologic approaches integrating the NSG-HIS mouse, non-human primates, and cancer patients for the development of novel immunomodulatory anticancer agents with human specificity.
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, motolimod (VTX 2337) / BMS
Enrollment open: Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - Dec 15, 2016
P1/2, N=53, Recruiting,
These results are the first to demonstrate the value of pharmacologic approaches integrating the NSG-HIS mouse, non-human primates, and cancer patients for the development of novel immunomodulatory anticancer agents with human specificity. Active, not recruiting --> Recruiting
- |||||||||| motolimod (VTX 2337) / BMS
Enrollment closed, Enrollment change, Immunomodulating, Metastases: TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors (clinicaltrials.gov) - Oct 19, 2016
P1, N=4, Active, not recruiting,
Active, not recruiting --> Recruiting Recruiting --> Active, not recruiting | N=20 --> 4
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, motolimod (VTX 2337) / BMS
Enrollment closed: Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - Aug 22, 2016
P1/2, N=53, Active, not recruiting,
Recruiting --> Active, not recruiting | N=20 --> 4 Recruiting --> Active, not recruiting
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Opdivo (nivolumab) / BMS, motolimod (VTX 2337) / BMS
Biomarker, Enrollment change, Trial primary completion date, PD(L)-1 Biomarker: A Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab (clinicaltrials.gov) - Jan 7, 2016
P1, N=24, Recruiting,
Initiation date: May 2016 --> Feb 2016 N=15 --> 24 | Trial primary completion date: Dec 2015 --> Dec 2016
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