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-

Login to view timeline

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

Login to view more data

100 Translational Medicine associated with TG-4010

Login to view more data

100 Patents (Medical) associated with TG-4010

Login to view more data

28

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

Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC

Q2 · MEDICINE

ArticleOA

Author: Nourtier, Virginie ; Quemeneur, Eric ; Gantzer, Murielle ; Grellier, Benoit ; Tosch, Caroline ; Bendjama, Kaïdre ; Barraud, Luc ; Limacher, Jean Marc ; Préville, Xavier ; Bastien, Bérangère

BACKGROUNDAdvanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine.METHODThe TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC. 78 patients from the TIME study carrying the HLA-A02*01 haplotype were analyzed using combinatorial encoding of MHC multimers to detect low frequencies of cellular immune responses to TG4010 and other unrelated TAA.RESULTSWe report that improvement of survival under TG4010 treatment correlated with development of T cell responses against MUC1. Interestingly, responses against MUC1 were associated with broadening of CD8 responses against non-targeted TAA, thus demonstrating induction of epitope spreading.CONCLUSIONOur results support the causality of specific T-cell response in improved survival in NSCLC. Additionally, vaccine induced epitope spreading to other TAA participates to the enrichment of the diversity of the anti-tumor response. Hence, TG4010 appears as a useful therapeutic option to maximize response rate and clinical benefit in association with other targeted immuno-modulators.TRIAL REGISTRATIONRegistered on ClinicalTrials.gov under identifier NCT01383148 on June 23rd, 2011.

100 Deals associated with TG-4010

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06584

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
metastatic non-small cell lung cancer	Phase 3	BE	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	BE	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

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

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	Nivolumab+TG4010	(frrgwwzuzs) = dsisriyjpp lwkeazbrqw (bpmlcyvheb, jcnorrfnji - joggequria) View more	-	11 Jan 2022
NCT01383148 (Pubmed \| Lancet Oncol) Manual	Phase 2/3	Non-Small Cell Lung Cancer First line	222	Chemotherapy+TG4010	(kdqpemozhe): HR = 0.77 View more	Positive	01 Feb 2016
				Chemotherapy+Placebo
TIME study (WCLC2015)	Not Applicable	Advanced Lung Non-Small Cell Carcinoma	222	TG4010	(qqwpiqhkeu) = urokwdecmg panwqzbnyy (hmivszxscb ) View more	Positive	08 Sep 2015
				Placebo	(qqwpiqhkeu) = ssutqperlf panwqzbnyy (hmivszxscb ) View more
NCT01383148 (TIME, ASCO2015)	Phase 3	metastatic non-small cell lung cancer	222	TG4010	(otlefgigqs): 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	(qlxxciwuld) = ynwdiqnmrv uxdwayhwle (nrtzldwtju ) View more	Positive	01 Nov 2011
				first-line chemotherapy	(qlxxciwuld) = zhcnbymxxe uxdwayhwle (nrtzldwtju ) View more
AACR2009	Phase 2	Non-Small Cell Lung Cancer	148	Arm 1 (TG4010 + chemotherapy)	(qvjbraqnqh) = ubnkmxohfp lcajdpkodd (gnwtbcfwus ) View more	-	01 May 2009
				Arm 2 (chemotherapy alone)	(qvjbraqnqh) = bvnzthljcg lcajdpkodd (gnwtbcfwus ) View more
ASCO2008	Phase 2	Non-Small Cell Lung Cancer	148	Cisplatin 75mg/m2 + Gemcitabine 1250mg/m2	(efrtdqzuzp) = utirpiqgrv somrdkpzbt (qxyvrzpjlp, 0.16–0.36)	-	20 May 2008
				Cisplatin 75mg/m2 + Gemcitabine 1250mg/m2 + TG4010	(efrtdqzuzp) = vmflubluxf somrdkpzbt (qxyvrzpjlp, 0.31–0.55)
ASCO2006	Phase 2	Metastatic Renal Cell Carcinoma	-	TG4010 alone	(cptfvknbxf) = vlrevwptqf ylgwaxtymq (svipdntjto, 10–27.9) View more	-	20 Jun 2006
				TG4010 in combination with cytokines	(cptfvknbxf) = ucesesajry ylgwaxtymq (svipdntjto, 6–26) View more
ASCO2005	Phase 2	Metastatic Renal Cell Carcinoma	37	TG4010 alone	(dsxiqknqbw) = hwdukoivrg ophytexsvg (guiyrwngjh, 62–89) View more	-	01 Jun 2005
				TG4010 + Interferon alpha-2a (INF) + Interleukin 2 (IL2)	(dsxiqknqbw) = mnqmzcrvbg ophytexsvg (guiyrwngjh, 40–77) View more
ASCO2005	Phase 2	Non-Small Cell Lung Cancer	65	TG4010 + cisplatin and vinorelbine	(rgdnkcdqey) = tcamsgkxjg lmejrprnxu (uchjpsqmsd )	-	01 Jun 2005
				TG4010 alone	(gnslnobmgs) = zihigtysdh ksopiidwpv (hzavakcxmp, 9.6–15.4) View more