- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics
Post-Intervention HIV Control Linked to Early In Vivo CD8+ T-Cell Proliferative Response to Rebound (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_1052;
P=N/A, P1/
To our knowledge, these studies are the first to demonstrate a relationship between the early in vivo CD8+ T cell proliferative response to viral reactivation and HIV control post-ART. The results support continued focus on developing HIV cure strategies that enhance HIV-specific CD8+ T cell proliferative capacity.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, VRC07-523LS / National Institute of Allergy and Infectious Diseases, IAVI, TaiMed Biologics
Effect of Broadly Neutralizing Antibody Exposure on HIV Rebound Following Combination Immunotherapy (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_950;
P1/2
Our results suggest that post-treatment setpoint was not driven by bNAb susceptibility and that the association of IQ90 and setpoint is driven by higher VRC07-523LS levels at the time of rebound in those who rebounded earlier and had higher setpoints. Overall, bNAb PK-PD is likely not responsible for lower observed post-treatment setpoints during this trial, suggesting the effect is likely attributable to changes in anti-HIV immune function.
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial completion date, Trial primary completion date, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - Oct 23, 2023
P1, N=28, Active, not recruiting,
Overall, bNAb PK-PD is likely not responsible for lower observed post-treatment setpoints during this trial, suggesting the effect is likely attributable to changes in anti-HIV immune function. Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2025
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Trial completion: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - May 23, 2023
P2a, N=47, Completed,
ClinicalTrials.gov identifier: NCT03837756 . Active, not recruiting --> Completed
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Lefitolimod (TLR agonist) and ipilimumab in patients with advanced solid tumors: A phase I trial. (On Demand | Hall A; Poster Bd # 406) - Apr 26, 2023 - Abstract #ASCO2023ASCO_2332;
The combination of high subcutaneous doses or intra-tumoral administration of lefitolimod in combination with ipilimumab is safe and well tolerated in patients with advanced cancers, with preliminary antitumor activity observed. Clinical trial information: NCT0266877.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
THE IMPACT OF 3BNC117; 10-1074; AND LEFITOLIMOD ON HIV-1 PERSISTENCE: THE TITAN TRIAL (Ballroom 1 (Level 5)) - Feb 13, 2023 - Abstract #CROI2023CROI_211;
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Biomarker, Journal, IO biomarker: CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy. (Pubmed Central) - Jul 30, 2022
Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment closed: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - Mar 31, 2022
P2a, N=47, Active, not recruiting,
Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment. Recruiting --> Active, not recruiting
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Enrollment change, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - Feb 15, 2022
P1, N=28, Active, not recruiting,
Recruiting --> Active, not recruiting N=55 --> 28
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial completion date, Trial primary completion date, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - Nov 2, 2021
P1, N=55, Active, not recruiting,
N=55 --> 28 Trial completion date: May 2021 --> May 2024 | Trial primary completion date: May 2021 --> May 2023
- |||||||||| Review, Journal: Current status of intralesional agents in treatment of malignant melanoma. (Pubmed Central) - Jul 20, 2021
This review focuses on the current status of IT agents currently under clinical trials in melanoma. Reviewed therapies include T-VEC, T-VEC with immune checkpoint inhibitors including ipilimumab and pembrolizumab or other agents, RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (coxsackievirus A21, CVA21) alone or in combination with checkpoint inhibitors, oncolytic polio/rhinovirus recombinant (PVSRIPO), MAGE-A3-expressing MG1 Maraba virus, VSV-IFNbetaTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (Telomelysin), Stimulation of Interferon Genes Pathway (STING agonists) including DMXAA, MIW815 (ADU-S100) and MK-1454, PV-10, toll-like receptors (TLRs) agonists including TLR-9 agonists (SD-101, CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (poly-ICLC), electroporation including calcium electroporation and plasmid interleukin-12 electroporation (pIL-12 EP), IT ipilimumab, INT230-6 (cisplatin and vinblastine with an amphiphilic penetration enhancer), TTI-621 (SIRPαFc), CD-40 agonistic antibodies (ABBV-927 and APX005M), antimicrobial peptide LL37 and other miscellaneous agents.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Trial completion date, Trial primary completion date: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - Apr 22, 2021
P2a, N=48, Recruiting,
Reviewed therapies include T-VEC, T-VEC with immune checkpoint inhibitors including ipilimumab and pembrolizumab or other agents, RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (coxsackievirus A21, CVA21) alone or in combination with checkpoint inhibitors, oncolytic polio/rhinovirus recombinant (PVSRIPO), MAGE-A3-expressing MG1 Maraba virus, VSV-IFNbetaTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (Telomelysin), Stimulation of Interferon Genes Pathway (STING agonists) including DMXAA, MIW815 (ADU-S100) and MK-1454, PV-10, toll-like receptors (TLRs) agonists including TLR-9 agonists (SD-101, CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (poly-ICLC), electroporation including calcium electroporation and plasmid interleukin-12 electroporation (pIL-12 EP), IT ipilimumab, INT230-6 (cisplatin and vinblastine with an amphiphilic penetration enhancer), TTI-621 (SIRPαFc), CD-40 agonistic antibodies (ABBV-927 and APX005M), antimicrobial peptide LL37 and other miscellaneous agents. Trial completion date: Feb 2021 --> Feb 2023 | Trial primary completion date: Jul 2020 --> Jul 2022
- |||||||||| TVGV-HB / Thevax Genetics Vaccine, lefitolimod (MGN1703) / Mologen, OncXerna Therap, iPharma
Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker: TLR9 activation cooperates with T cell checkpoint blockade to regress poorly immunogenic melanoma. (Pubmed Central) - Jul 22, 2020
Using both a TLR9 agonist (MGN1703) and a CTLA-4 antibody (9D9-IgG2a) of increased potency cured 50% of bi-lateral B16-F10 melanoma. These findings suggest that intra-tumoral TLR9 agonists can improve sensitivity of poorly immunogenic tumors to T cell checkpoint blockade, and that newer, higher potency TLR agonists and checkpoint antibodies can raise the therapeutic ceiling for this combination therapy.
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Enrollment closed, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - Jul 20, 2020
P1, N=55, Active, not recruiting,
These findings suggest that intra-tumoral TLR9 agonists can improve sensitivity of poorly immunogenic tumors to T cell checkpoint blockade, and that newer, higher potency TLR agonists and checkpoint antibodies can raise the therapeutic ceiling for this combination therapy. Recruiting --> Active, not recruiting
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial completion date, Trial primary completion date, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - Nov 14, 2019
P1, N=60, Recruiting,
These properties of potent immune surveillance reactivation render lefitolimod an ideal candidate as therapeutic agent for immuno-oncology, e.g. improving CPI strategies. Trial completion date: May 2020 --> May 2021 | Trial primary completion date: May 2019 --> May 2021
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment open: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - May 7, 2019
P2a, N=48, Recruiting,
Hence, and given its mode of action, lefitolimod will be evaluated in combination with other anti-cancer immunotherapies. Not yet recruiting --> Recruiting
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
New P2a trial: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - Feb 11, 2019
P2a, N=48, Not yet recruiting,
- |||||||||| lefitolimod (MGN1703) / Mologen, OncXerna Therap, iPharma
Journal, IO biomarker: The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon. (Pubmed Central) - Dec 14, 2018
TLR9 expression at baseline was inversely proportional to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.Mucosal Immunology advance online publication, 02 August 2017; doi:10.1038/mi.2017.59.
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial completion date, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - Oct 5, 2018
P1, N=60, Recruiting,
In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.Mucosal Immunology advance online publication, 02 August 2017; doi:10.1038/mi.2017.59. Trial completion date: May 2020 --> May 2019
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Trial completion, Phase classification, Enrollment change, Trial primary completion date, IO biomarker: TEACH: Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection (clinicaltrials.gov) - Jun 29, 2017
P1b/2a, N=12, Completed,
Active, not recruiting --> Completed Enrolling by invitation --> Completed | Phase classification: P1/2 --> P1b/2a | N=16 --> 12 | Trial primary completion date: Jan 2017 --> Jun 2017
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment closed, Trial primary completion date, Immunomodulating, Metastases: IMPALA: Evaluation of MGN1703 Maintenance Treatment in Patients With mCRC With Tumor Reduction During Induction Treatment (clinicaltrials.gov) - Jun 22, 2017
P3, N=540, Active, not recruiting,
Enrolling by invitation --> Completed | Phase classification: P1/2 --> P1b/2a | N=16 --> 12 | Trial primary completion date: Jan 2017 --> Jun 2017 Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2017 --> Mar 2019
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Trial primary completion date, Immunomodulating: IMPULSE: Randomized Study of Maintenance Therapy With MGN1703 in Patients With SCLC (clinicaltrials.gov) - Mar 23, 2017
P2, N=102, Active, not recruiting,
Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2017 --> Mar 2019 Trial primary completion date: Mar 2017 --> Nov 2016
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Enrollment open, Trial initiation date, Trial primary completion date, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - May 13, 2016
P1, N=60, Recruiting,
Trial primary completion date: Mar 2017 --> Nov 2016 Not yet recruiting --> Recruiting | Initiation date: Aug 2016 --> May 2016 | Trial primary completion date: Aug 2019 --> May 2019
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial initiation date, Trial primary completion date, Metastases: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - May 4, 2016
P1, N=60, Not yet recruiting,
Not yet recruiting --> Recruiting | Initiation date: Aug 2016 --> May 2016 | Trial primary completion date: Aug 2019 --> May 2019 Initiation date: Mar 2016 --> Aug 2016 | Trial primary completion date: Mar 2019 --> Aug 2019
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment open, Trial primary completion date, IO biomarker: TEACH: Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection (clinicaltrials.gov) - Mar 15, 2016
P1/2, N=16, Enrolling by invitation,
Initiation date: Mar 2016 --> Aug 2016 | Trial primary completion date: Mar 2019 --> Aug 2019 Active, not recruiting --> Enrolling by invitation | Trial primary completion date: May 2016 --> Jan 2017
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment closed, Immunomodulating: IMPULSE: Randomized Study of Maintenance Therapy With MGN1703 in Patients With SCLC (clinicaltrials.gov) - Nov 8, 2015
P2, N=100, Active, not recruiting,
Active, not recruiting --> Enrolling by invitation | Trial primary completion date: May 2016 --> Jan 2017 Recruiting --> Active, not recruiting
- |||||||||| lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment closed, IO biomarker: TEACH: Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection (clinicaltrials.gov) - Sep 18, 2015
P1/2, N=16, Active, not recruiting,
Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting
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