Delving into the Latest Updates on TG-4010 with Synapse

Overview

Basic Info

Drug Type

Recombinant vector vaccine, Therapeutic vaccine

Synonyms

Cancer vaccine, Mesmulogene Ancovacivec

+ [2]

Target

IL-2 x MUC1

Mechanism

IL-2 stimulants(Interleukin-2 stimulants), MUC1 stimulants(Mucin-1 stimulants)

Therapeutic Areas

NeoplasmsRespiratory DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Adenocarcinoma of prostateAdvanced Lung Non-Small Cell Carcinomametastatic non-small cell lung cancer+ [6]

Originator Organization

Transgene SA

Active Organization-

Inactive Organization

Transgene SA

Bristol Myers Squibb Co.

Drug Highest PhaseDiscontinuedPhase 2/3

First Approval Date-

Regulation-

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This phase II trial studies how well TG4010 and nivolumab work in previously treated patients with non-small cell lung cancer. Vaccines that are made from a gene-modified virus, such as TG4010, may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as nivolumab, interfere with the ability of tumor cells to grow and spread. Giving TG4010 and nivolumab together may work better in previously treated patients with non-small cell lung cancer.

Start Date14 Dec 2016

Sponsor / Collaborator

University of California, Davis

[+3]

100 Clinical Results associated with TG-4010

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100 Translational Medicine associated with TG-4010

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100 Patents (Medical) associated with TG-4010

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31

Literatures (Medical) associated with TG-4010

14 Feb 2019·Current Cancer Drug TargetsQ4 · MEDICINE

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

Q4 · MEDICINE

Review

Author: Chen, Chen ; Yang, Lei ; Liu, Zi-Ling ; Li, Zhi ; Cong, Xiao-Feng ; Zhao, Sha-Sha ; Ren, Meng ; Yan, Bing-Di

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

02 Jan 2018·Human Vaccines & ImmunotherapeuticsQ3 · MEDICINE

Sequential administration of MVA-based vaccines and PD-1/PD-L1-blocking antibodies confers measurable benefits on tumor growth and survival: Preclinical studies with MVA-βGal and MVA-MUC1 (TG4010) in a murine tumor model

Q3 · MEDICINE

Article

Author: Nourtier, Virginie ; Sansas, Benoit ; Hortelano, Julie ; Remy-Ziller, Christelle ; Bendjama, Kaïdre ; Gantzer, Murielle ; Claudepierre, Marie-Christine ; Préville, Xavier ; Rittner, Karola ; Quemeneur, Eric ; Thioudellet, Christine

TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal. Mice showed increased survival rates after repeated intravenous injections of TG4010 or MVA-βgal, compared to an empty MVA control vector. Treatment with MVA vectors led to the accumulation of CD3^dimCD8^dim T cells, with two subpopulations characterized as KLRG1⁺CD127^- short-lived effector cells (SLECs), and KLRG1^-CD127^- early effector cells (EECs) comprising cells releasing IFNγ, Granzyme B and CD107a upon antigen-specific peptide stimulation. EECs were characterized by an up-regulation of PD-1. Tumor growth in the diseased lung correlated with the appearance of PD1⁺ Treg cells that partially disappeared after TG4010 treatment. At late stage of tumor development in the lung, PD-L1 was detected on CD45^- tumor cells, on CD4⁺ cells, including Treg cells, on CD3⁺CD8⁺ and CD3^dimCD8^dim T lymphocytes, on NK cells, on MDSCs and on alveolar macrophages. We demonstrated that targeting the PD-1/PD-L1 pathway with blocking monoclonal antibodies several days after TG4010 treatment, at late stage of tumor development, enhanced the therapeutic protection induced by the vaccine, supporting the ongoing clinical evaluation of TG4010 immunotherapy in combination with Nivolumab.

01 Dec 2017·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen

Q2 · MEDICINE

ArticleOA

Author: Joseph T. Rakowski ; Lyndsey A. Reich ; Lisa M. Abernathy ; Philippe Slos ; Kali Hankerd ; Gilda G. Hillman ; Eric Quemeneur ; Matthew D. Fountain ; Christopher K. Yunker ; Shoshana E. Rothstein

BACKGROUNDWe previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal adenocarcinoma (Renca) cells transfected with MUC1.METHODSEstablished subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation. Growth delays were monitored by tumor measurements and histological responses were evaluated by immunohistochemistry. Specific immunity was assessed by challenge with Renca-MUC1 cells. Generation of tumor-specific T cells was detected by IFN-γ production from splenocytes stimulated in vitro with tumor lysates using ELISPOT assays.RESULTSTumor growth delays observed by tumor irradiation combined with MVA-MUC1-IL-2 vaccine were significantly more prolonged than those observed by vaccine, radiation, or radiation with MVA empty vector. The sequence of cancer vaccine followed by radiation two days later resulted in 55-58% complete responders and 60% mouse long-term survival. This sequence was more effective than that of radiation followed by vaccine leading to 24-30% complete responders and 30% mouse survival. Responding mice were immune to challenge with Renca-MUC1 cells, indicating the induction of specific tumor immunity. Histology studies of regressing tumors at 1 week after therapy, revealed extensive tumor destruction and a heavy infiltration of CD45⁺ leukocytes including F4/80⁺ macrophages, CD8⁺ cytotoxic T cells and CD4⁺ helper T cells. The generation of tumor-specific T cells by combined therapy was confirmed by IFN-γ secretion in tumor-stimulated splenocytes. An abscopal effect was measured by rejection of an untreated tumor on the contralateral flank to the tumor treated with radiation and vaccine.CONCLUSIONSThese findings suggest that cancer vaccine given prior to local tumor irradiation augments an immune response targeted at tumor antigens that results in specific anti-tumor immunity. These findings support further exploration of the combination of radiotherapy with cancer vaccines for the treatment of cancer.

100 Deals associated with TG-4010

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
metastatic non-small cell lung cancer	Phase 3	IL	Transgene SA	01 Apr 2012
metastatic non-small cell lung cancer	Phase 3	GB	Transgene SA	01 Apr 2012
metastatic non-small cell lung cancer	Phase 3	IL	Transgene SA	01 Apr 2012
metastatic non-small cell lung cancer	Phase 3	ES	Transgene SA	01 Apr 2012
metastatic non-small cell lung cancer	Phase 3	GB	Transgene SA	01 Apr 2012
metastatic non-small cell lung cancer	Phase 3	ES	Transgene SA	01 Apr 2012
Advanced Lung Non-Small Cell Carcinoma	Phase 3	DE	Transgene SA	01 Dec 2005
Advanced Lung Non-Small Cell Carcinoma	Phase 3	PL	Transgene SA	01 Dec 2005
Advanced Lung Non-Small Cell Carcinoma	Phase 3	HU	Transgene SA	01 Dec 2005
Advanced Lung Non-Small Cell Carcinoma	Phase 3	FR	Transgene SA	01 Dec 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03353675 (CTgov)	Phase 2	metastatic non-small cell lung cancer \| Squamous non-small cell lung cancer	44	Chemotherapy+Nivolumab+TG4010	(oevmriggqa) = pgsmersxmf fhzzxcurgu (ecmphipccd, nthpgfutrq - jnliljydjb) View more	-	11 Jan 2022
NCT01383148 (Pubmed \| Lancet Oncol) Manual	Phase 2/3	Non-Small Cell Lung Cancer First line	222	Chemotherapy+TG4010	(dmsbvikwty): HR = 0.77 View more	Positive	01 Feb 2016
				Chemotherapy+Placebo
TIME study (WCLC2015)	Not Applicable	Advanced Lung Non-Small Cell Carcinoma	222	TG4010	(zcfyljtdqh) = zyvdzvvabz hxjefkloqx (yaviqaprgb ) View more	Positive	08 Sep 2015
				Placebo	(zcfyljtdqh) = wjjeeildda hxjefkloqx (yaviqaprgb ) View more
NCT01383148 (TIME, ASCO2015)	Phase 3	metastatic non-small cell lung cancer	222	TG4010	(ztvgdmrdvk): HR = 0.66 (95% CI, 0.46 - 0.95), P-Value = 0.013	Positive	20 May 2015
				Placebo
NCT00415818 (Pubmed \| Lancet Oncol) Manual	Phase 2	Non-Small Cell Lung Cancer First line	148	first-line chemotherapy+TG4010	(xshhafmiku) = kkwncudmvd yglhzedugy (kgzubxbpuz ) View more	Positive	01 Nov 2011
				first-line chemotherapy	(xshhafmiku) = rcstoznjda yglhzedugy (kgzubxbpuz ) View more
AACR2009	Phase 2	Non-Small Cell Lung Cancer	148	Arm 1 (TG4010 + chemotherapy)	(vimwcpvmso) = hjreilwoqf zujjvgznui (kbpwdwxipb ) View more	-	01 May 2009
				Arm 2 (chemotherapy alone)	(vimwcpvmso) = dxthuamnyw zujjvgznui (kbpwdwxipb ) View more
ASCO2008	Phase 2	Non-Small Cell Lung Cancer	148	Cisplatin 75mg/m2 + Gemcitabine 1250mg/m2	(bvtswcswno) = uvcarqrgkz txdcdhmnvr (ftvalgcxqs, 0.16–0.36)	-	20 May 2008
				Cisplatin 75mg/m2 + Gemcitabine 1250mg/m2 + TG4010	(bvtswcswno) = awypxwejuj txdcdhmnvr (ftvalgcxqs, 0.31–0.55)
ASCO2006	Phase 2	Metastatic Renal Cell Carcinoma	-	TG4010 alone	(ldlgjfdbmt) = hgdnmurkgr cvfvfiyzpy (binqqomyzq, 10–27.9) View more	-	20 Jun 2006
				TG4010 in combination with cytokines	(ldlgjfdbmt) = ljadgzuwsy cvfvfiyzpy (binqqomyzq, 6–26) View more
ASCO2005	Phase 2	Metastatic Renal Cell Carcinoma	37	TG4010 alone	(apcnisdqhc) = uzljkbjqvo tosjxzllcx (sifnhutmlc, 62–89) View more	-	01 Jun 2005
				TG4010 + Interferon alpha-2a (INF) + Interleukin 2 (IL2)	(apcnisdqhc) = jvaqrnqnjf tosjxzllcx (sifnhutmlc, 40–77) View more
ASCO2005	Phase 2	Non-Small Cell Lung Cancer	65	TG4010 + cisplatin and vinorelbine	(mrumvieeig) = unuyhazwnl nuedqgsxkl (wzahinancq )	-	01 Jun 2005
				TG4010 alone	(svxafaslqe) = pnqdoqghjb zvhuoltnex (loxqxfgopo, 9.6–15.4) View more