Delving into the Latest Updates on Belagenpumatucel-L with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine, Cell therapy

Synonyms

Belagenpumatucel-L (USAN), Glionix, Ranagengliotucel-T

+ [2]

Target

TGF-β2

Action

inhibitors

Mechanism

TGF-β2 inhibitors(Transforming growth factor beta 2 inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication-

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaBronchogenic Carcinomametastatic non-small cell lung cancer+ [2]

Originator Organization

The Sidney Kimmel Comprehensive Cancer Center

Active Organization-

Inactive Organization

Activate Immunotherapy

License Organization-

Drug Highest PhasePendingPhase 3

First Approval Date-

RegulationOrphan Drug (United States)

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Phase III Study of Lucanix™ (Belagenpumatucel-L) in Advanced Non-small Cell Lung Cancer: An International Multicenter, Randomized, Double-blinded, Placebo-controlled Study of Lucanix™ Maintenance Therapy for Stages III/IV NSCLC Subjects Who Have Responded to or Have Stable Disease Following One Regimen of Front-line, Platinum-based Combination Chemotherapy

Rationale: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than a placebo as maintenance therapy in treatment of subjects with non-small cell lung cancer.
Purpose: This randomized phase III trial is studying vaccine therapy to see how well it works compared with a placebo in treating subjects with stage III or stage IV non-small cell lung cancer.

Start Date01 Jul 2008

Sponsor / Collaborator

Activate Immunotherapy

NCT01058785

/ CompletedPhase 2

Phase II Study of Lucanix™ (TGF-beta2 Antisense Gene Modified Allogeneic Tumor Cell Vaccine) in Patients With Stages II-IV Non-Small Cell Lung Cancer

In this Phase II clinical trial the investigators will use four human non-small cell lung cancer cell lines that have been previously established in tissue culture laboratory. The investigators will gene modify these tumor cells in the laboratory to block their TGF-beta secretion. The investigators will inject the genetically engineered cells as vaccines in patients with stages II to IV non-small cell lung cancer. Our rationale for using other people's tumor cells is that lung tumor cell lines belonging to different people have been shown to share common characteristics that are recognized by non-self immune systems.

Start Date01 Mar 2003

Sponsor / Collaborator

Activate Immunotherapy

NCT01279798

/ No longer availableNot Applicable

Expanded Access Multicenter Study of Lucanix® (Belagenpumatucel-L) in Advanced Non-small Cell Lung Cancer.

This is an expanded access protocol designed to make Lucanix® available to subjects with advanced non-small cell lung cancer (NSCLC) who are not eligible for the Phase III Protocol, NR001-03. A total of 45 patients will be enrolled into the study.

Start Date-

Sponsor / Collaborator

Activate Immunotherapy

100 Clinical Results associated with Belagenpumatucel-L

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100 Translational Medicine associated with Belagenpumatucel-L

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100 Patents (Medical) associated with Belagenpumatucel-L

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22

Literatures (Medical) associated with Belagenpumatucel-L

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: Zhao, Sha-Sha ; Ren, Meng ; Liu, Zi-Ling ; Li, Zhi ; Chen, Chen ; Yang, Lei ; Cong, Xiao-Feng ; 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.

01 Nov 2015·Annals of oncology : official journal of the European Society for Medical OncologyQ1 · MEDICINE

Why has active immunotherapy not worked in lung cancer?

Q1 · MEDICINE

Review

Author: Thomas, A ; Giaccone, G

Vaccines that rely on active specific stimulation of the host immune system have the potential to trigger durable antitumor responses with minimal toxicity. However, in nonsmall-cell lung cancer (NSCLC), several large phase III trials of vaccines reported within the last year have yielded disappointing results. Compared with placebo, belagenpumatucel-L (an allogenic tumor cell vaccine), tecemotide (a peptide vaccine targeting MUC-1) and melanoma-associated antigen-A3 (a protein-based vaccine) did not improve outcomes in NSCLC. The lack of clinically significant outcomes, despite their ability to prime and expand tumor antigen-specific T cells could at least partly be attributed to the inability of vaccine-induced T-cell responses to overcome the tumoral mechanisms of immune escape which limit the clonal expansion of T cells following vaccination. A number of such mechanisms have been recognized including reduced antigen presentation, antigenic loss, cytokines, immunosuppressive cells and immune checkpoints. Strategies aimed at modulating the immune checkpoints have shown promise and are on the verge of revolutionizing the therapeutic landscape of metastatic NSCLC. Overcoming immune tolerance and improving the activation of antitumor T cells via combinatorial approaches may represent a new and more promising therapeutic application for active immunotherapies in NSCLC.

01 Nov 2015·European journal of cancer (Oxford, England : 1990)Q1 · MEDICINE

A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer

Q1 · MEDICINE

Article

Author: Dunlop, D J ; Moses, S C ; Jain, M ; Tan, M ; Garon, E B ; van den Heuvel, M M ; Nemunaitis, J ; Shawler, D L ; Juhász, E ; Bazhenova, L A ; Kloecker, G H ; Chu, Q ; Davis, C S ; Carrier, E ; Lal, R ; Giaccone, G ; Eaton, K D ; Ramlau, R ; Fakhrai, H

BACKGROUND:

Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment.

METHODS:

Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival.

RESULTS:

This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032).

CONCLUSIONS:

Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.

100 Deals associated with Belagenpumatucel-L

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External Link

KEGG	Wiki	ATC	Drug Bank
D06563	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Lung Non-Small Cell Carcinoma	Phase 3	United States	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	Canada	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	Hungary	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	India	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	Netherlands	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	Poland	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	Serbia	Activate Immunotherapy	01 Jul 2008
Advanced Lung Non-Small Cell Carcinoma	Phase 3	United Kingdom	Activate Immunotherapy	01 Jul 2008
metastatic non-small cell lung cancer	Phase 3	United States	Activate Immunotherapy	01 Jul 2008
metastatic non-small cell lung cancer	Phase 3	Canada	Activate Immunotherapy	01 Jul 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00676507 (Pubmed \| Eur J Cancer)	Phase 3	Non-Small Cell Lung Cancer Maintenance	-	Belagenpumatucel-L	ownkbijisp(xnplabzgja) = lfufspkrxr zmvtdadqjf (cqbydhqhmw ) View more	-	01 Nov 2015
NCT00676507 (Pubmed \| Eur J Cancer)	Phase 3	Non-Small Cell Lung Cancer Maintenance	-	Placebo	ownkbijisp(xnplabzgja) = dghoraffdq zmvtdadqjf (cqbydhqhmw ) View more	-	01 Nov 2015
Phase III Study of Belagenpumatucel-L (ASGCT2014)	Phase 3	Non-Small Cell Lung Cancer Maintenance	532	Belagenpumatucel-L	ccaykppshw(wzpjarwego) = tosndzikvy nuemsnqzgv (fwhapbybwt )	Positive	01 May 2014
Phase III Study of Belagenpumatucel-L (ASGCT2014)	Phase 3	Non-Small Cell Lung Cancer Maintenance	532	Belagenpumatucel-L (Placebo)	ccaykppshw(wzpjarwego) = tjidmydwqc nuemsnqzgv (fwhapbybwt )	Positive	01 May 2014
AACR2012	Phase 2	Non-Small Cell Lung Cancer	36	Belagenpumatucel-L	juyzlbbrwg(tequzcqivv) = gxewcdzogz dmzuccdhge (iojwekbqvg, 25.2 - 39.8)	-	15 Apr 2012
Phase II Trial of Belagenpumatucel-L (ASGCT2009)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	21	Belagenpumatucel-L	eahgftvhtr(jzelcllznn) = aztaalehxe zmqulhrsqp (iuuyyfgcxv )	Positive	01 May 2009