Delving into the Latest Updates on Golnerminogene pradenovec with Synapse

Overview

Basic Info

Drug Type

Gene therapy

Synonyms

Golnerminogene pradenovec (USAN/INN)

+ [1]

Target

TNF-α

Mechanism

TNF-α stimulants(Tumor necrosis factor α stimulants), Gene transference

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [2]

Active Indication-

Inactive Indication

Esophageal CarcinomaLocally Advanced Prostate CarcinomaMetastatic melanoma+ [5]

Originator Organization

Asahi Kasei Corp.

Active Organization-

Inactive Organization

GenVec, Inc.

National Institutes of Health

Asahi Kasei Corp.

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Gene Sequence

Sequence Code 556128468

The primary purpose of this study is to assess the safety and feasibility of giving TNFerade™ with 5-FU, Cisplatin and radiation therapy to patients with locally advanced, esophageal cancer prior to surgical resection. TNFerade™ is a replication deficient (E1, E3 and E4 deleted) adenovirus vector containing the gene for TNF-alpha controlled by a radiation inducible promoter. This allows the expression of TNF-alpha to be greatest in the area receiving radiation. TNF-alpha is a potent cytokine that has been shown to have potent anti-cancer activities but, due to systemic toxicity, could not be delivered at effective doses. TNFerade™ is a novel way of selective delivery of TNF-alpha to tumor cells.
TNFerade™ will be delivered once a week for five weeks by direct intratumoral injection by using endoscopy or Endoscopic Ultrasound. 5-FU (1000 mg/m2/day) will be delivered via continuous infusion for 96 hours during weeks 1 and 4. Cisplatin (75 mg/m2) will be delivered on Day 1 and Day 29 intravenously. The dose of radiation delivered will be 45 Gy in 1.8 Gy fractions for 5 weeks.

Start Date-

Sponsor / Collaborator

GenVec, Inc.

NCT01048151 / Unknown statusPhase 1

A PHASE I SAFETY AND TOLERABILITY TRIAL OF RADIOTHERAPY, ANDROGEN DEPRIVATION, AND INTRATUMORAL INJECTIONS OF AdGVEGR.TNF.11D (TNFeradeTM) FOR PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

While radiation therapy with androgen ablation (hormone reduction) is the standard method of treating locally advanced prostate cancer. New treatments are being combined with radiation therapy in an effort to further improve the cure rates.
This study proposes to combine an experimental drug, TNFerade™ Biologic, (also called AdGVEGR.TNF.11D or "TNFerade") at different dose (amounts) levels in combination with radiation.
TNFerade™ Biologic is a form of gene transfer therapy that when injected into the tumor has shown to increase the effect of radiation therapy.

Start Date-

Sponsor / Collaborator

GenVec, Inc.

[+1]

NCT00496535 / CompletedPhase 1/2

A Phase I/II Safety, Tolerability, and "Proof of Concept" Study of TNFerade™ Biologic in Combination With Concomitant Radiotherapy, Fluorouracil, and Hydroxyurea (TNF-FHX) for Patients With Unresectable Recurrent Head and Neck Cancer

The primary objective of the first phase is to determine the safety, the maximum tolerated dose (MTD) and dose-limiting toxicity of TNFerade in combination with the previously studied combination of Fluorouracil (5FU), Hydroxyurea (HU) and standard daily radiotherapy in patients with recurrent head and neck cancer (RHNC). All chemoradiotherapy is administered on a "week-on/week-off" schedule. The primary objective of the second phase II is to determine the locoregional control rate at 24 months.

Start Date-

Sponsor / Collaborator

GenVec, Inc.

100 Clinical Results associated with Golnerminogene pradenovec

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100 Translational Medicine associated with Golnerminogene pradenovec

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100 Patents (Medical) associated with Golnerminogene pradenovec

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25

Literatures (Medical) associated with Golnerminogene pradenovec

01 Jan 2015·Indian Journal of PharmacologyQ4 · MEDICINE

TNFerade, an innovative cancer immunotherapeutic

Q4 · MEDICINE

Review

Author: Kali, Arunava

Tumor necrosis factor-α (TNF-α) is a chemokine with effective tumoricidal properties. However, severe systemic toxicity limits its use of as anticancer agent. TNFerade is a novel replication deficient adenovector based gene therapy, which enables the radiation inducible translation of human TNF-α gene specifically in cancer cells. When injected intratumorally, it has least systemic distribution. Consequently, it lacks TNF-α related systemic toxicity. Evidence suggests that it has superior tumoricidal activity and tolerability with minimum adverse effects. It has demonstrated its beneficial role in the treatment of a variety of cancers in terms of improving the disease free and overall survival, delaying tumor progression, and inducing tumor regression when used with concurrent radiotherapy or chemotherapy.

01 Mar 2013·Annals of OncologyQ1 · MEDICINE

A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation

Q1 · MEDICINE

Article

Author: T. Darga ; E. A. Blair ; J. K. Salama ; M. W. Lingen ; T. Y. Seiwert ; E. E. Vokes ; R. R. Weichselbaum ; V. Villaflor ; K. Stenson ; D. Haraf ; E. E. W. Cohen ; M. E. Witt

BACKGROUNDAdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC).METHODSTNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 × 10(9) to 4 × 10(11) PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment.RESULTSFourteen patients were treated. DLT was reached at a dose level of 3 (4 × 10(11) PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient.CONCLUSIONSTNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 × 10(10) PU. Monitoring for thrombotic events is indicated.

01 Mar 2013·Journal of Clinical OncologyQ1 · MEDICINE

Randomized Phase III Multi-Institutional Study of TNFerade Biologic With Fluorouracil and Radiotherapy for Locally Advanced Pancreatic Cancer: Final Results

Q1 · MEDICINE

Article

Author: Canto, Marcia I. ; Laheru, Daniel A. ; Taylor, Gretchen E. ; Herman, Joseph M. ; Wolfgang, Christopher L. ; Ziegler, Mark A. ; Wang, Hao ; Shah, Raj J. ; Wild, Aaron T. ; Chang, Kenneth J. ; Donehower, Ross C. ; Cai, Hongyan ; Rosemurgy, Alexander ; Reid, Tony ; Savage, Dionne T. ; Hoffe, Sarah E. ; Klapman, Jason ; Tran, Phuoc T. ; Pawlik, Timothy M.

Purpose TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy. Patients and Methods In all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m2 per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 1011 particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m2 intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity. Results The analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P > .05). Conclusion SOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.

100 Deals associated with Golnerminogene pradenovec

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Prostate Carcinoma	Phase 3	US	GenVec, Inc.	13 Jan 2010
Locally Advanced Prostate Carcinoma	Phase 3	US	National Institutes of Health	13 Jan 2010
Recurrent Head and Neck Carcinoma	Phase 3	US	GenVec, Inc.	04 Jul 2007
Metastatic melanoma	Phase 3	US	GenVec, Inc.	05 Dec 2005
Rectal Cancer	Phase 3	US	GenVec, Inc.	30 Aug 2005
Pancreatic carcinoma non-resectable	Phase 3	US	GenVec, Inc.	13 Jan 2003
Esophageal Carcinoma	Phase 3	US	GenVec, Inc.	-
Pancreatic Cancer	Phase 3	-	Asahi Kasei Corp.	-
Pancreatic Cancer	Phase 3	-	National Cancer Institute	-
Sarcoma	Phase 3	US	GenVec, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00051480 (Pubmed \| Gastrointest Endosc)	Phase 1	Locally Advanced Malignant Neoplasm Neoadjuvant	-	TNFerade biologic	(xvhznrkqog) = bgmehscyka nxunbeoysb (zprlcqwmrh )	-	01 Jun 2012
ASCO2012	Phase 3	Locally Advanced Pancreatic Adenocarcinoma	277	TNFerade biologic + standard of care	mfurtpbnyt(wzbnibzdrf) = TNF resulted in more grade 1-2 fever/chills (p<0.001) than SOC gcuhosdxmy (eaumdptktc ) View more	Negative	20 May 2012
				Standard of care
PACT (ASCO2007)	Phase 2/3	Locally Advanced Pancreatic Adenocarcinoma	330	TNFerade + SOC	(ldyxcsqktx) = mrydswargp hywzhxqbxm (ihdrvdfvoc ) View more	-	20 Jun 2007
				SOC	(ldyxcsqktx) = dgfrnceogb hywzhxqbxm (ihdrvdfvoc ) View more
ASGCT2007	Not Applicable	Locally Advanced Malignant Neoplasm	-	TNFerade + chemoradiotherapy	ryxfjqfxye(telqxozqnx) = pqamqekllf smgtldgazi (ejlnaskdld ) View more	-	01 May 2007
				chemo-radiotherapy	ryxfjqfxye(telqxozqnx) = mzosaebzlk smgtldgazi (ejlnaskdld )
phase II study in 50 patients with locally advanced (non-resectable) pancreatic adenocarcinoma (ASGCT2006)	Phase 2	Pancreatic Cancer	50	TNFerade	(kxhvrwtohr) = kdkjghbdvo vmckrbgoqi (lzgudooffo, 4x10E11) View more	Positive	01 Aug 2006
The PACT (ASCO2006)	Phase 2	Locally Advanced Pancreatic Adenocarcinoma	74	TNFerade + CRT	(ytthpwccgu) = 63% iwjimflkbs (fnmwggxfjv ) View more	-	20 Jun 2006
ASCO2004	Not Applicable	Pancreatic carcinoma non-resectable	37	TNFerade	(rdwojosohp) = uhvvovhagv yomvrcxupp (yugqoxtoka )	-	15 Jul 2004
				Chemoradiation	(rdwojosohp) = qymswoygzh yomvrcxupp (yugqoxtoka )