Delving into the Latest Updates on NSC-733972 with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

Target

IL-12R

Mechanism

IL-12R stimulants(Interleukin-12 receptor stimulants)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases

Active Indication

Glioblastoma MultiformeGliosarcomaRecurrent Malignant Glioma

Inactive Indication-

Originator Organization

The University of Alabama at Birmingham

Active Organization

The University of Alabama at Birmingham

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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This Phase I (Cohort I and Cohort II) and Phase II trial is designed to confirm the safety and tolerability of Pembrolizumab when given in conjunction with M032, an Oncolytic Herpes Simplex Virus (oHSV) that expresses IL-12 and perform the Phase II portion using a Recommended Phase 2 Dose (RP2D) of M032 (provided by the Phase I) when given in conjunction with Pembrolizumab for recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or glio-sarcoma).

Start Date25 Feb 2022

Sponsor / Collaborator

The University of Alabama at Birmingham

NCT02062827 / Active, not recruitingPhase 1IIT

A Phase 1 Study of M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients With Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma

To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who would benefit from surgical resection of recurrent glioma

Start Date25 Nov 2013

Sponsor / Collaborator

The University of Alabama at Birmingham

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100 Clinical Results associated with NSC-733972

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100 Translational Medicine associated with NSC-733972

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100 Patents (Medical) associated with NSC-733972

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6

Literatures (Medical) associated with NSC-733972

01 Jun 2024·Journal of NeuroVirology

A viral attack on brain tumors: the potential of oncolytic virus therapy

Review

Author: Mokhtarpour, Kasra ; Rezaei, Nima ; Akbarzadehmoallemkolaei, Milad

Managing malignant brain tumors remains a significant therapeutic hurdle that necessitates further research to comprehend their treatment potential fully. Oncolytic viruses (OVs) offer many opportunities for predicting and combating tumors through several mechanisms, with both preclinical and clinical studies demonstrating potential. OV therapy has emerged as a potent and effective method with a dual mechanism. Developing innovative and effective strategies for virus transduction, coupled with immune checkpoint inhibitors or chemotherapy drugs, strengthens this new technique. Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors.

01 Feb 2021·Neurosurgical FocusQ2 · MEDICINE

Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas

Q2 · MEDICINE

Article

Author: Koehler, Jennifer W. ; Omar, Nidal B. ; Bentley, R. Timothy ; Gillespie, G. Yancey ; Platt, Simon R. ; Rissi, Daniel R. ; Crossman, David K. ; Yanke, Amy B. ; Sorjonen, Donald ; Shores, Andy ; Chambers, Melissa R. ; Markert, James M. ; Foote, Jeremy B.

OBJECTIVEThe diagnosis of glioma remains disheartening in the clinical realm. While a multitude of studies and trials have shown promise, improvements in overall survival have been disappointing. Modeling these tumors in the laboratory setting has become increasingly challenging, given their complex in situ behavior and interactions for therapeutic evasion. Dogs, particularly brachycephalic breeds, are known to spontaneously develop gliomas that resemble human gliomas both clinically and pathophysiologically, making canines with sporadic tumors promising candidates for study. Typically, survival among these dogs is approximately 2 months with palliation alone.METHODSThe authors have completed the first stage of a unique phase I dose-escalating canine clinical trial in which the safety and tolerability of M032, a nonneurovirulent oncolytic herpes simplex virus–1 vector genetically engineered to express interleukin-12, are being studied in pet dogs with gliomas undergoing maximum safe tumor resection and inoculation of the cavity with the viral infusate.RESULTSTwenty-five canine patients were enrolled between January 2018 and August 2020. One patient was electively withdrawn from the trial by its owner, and 3 did not receive the virus. For the 21 dogs that remained, 13 had high-grade gliomas, 5 had low-grade gliomas, and 3 were undetermined. According to histopathological analysis, 62% of the tumors were oligodendrogliomas. At the time of this report, the median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities have been observed to date.CONCLUSIONSIn this largest study of oncolytic viral therapy for canine brain tumors to date, treatment with M032 did not cause harm and the combination of surgery and oncolytic viral therapy may have contributed to prolonged survival in pet dogs with spontaneous gliomas. Forthcoming in-depth radiographic, immunohistochemical, and genetic analyses will afford a more advanced understanding of how this treatment impacts these tumors and the immune system. Our goal is to utilize these findings bitranslationally to inform human studies and refine therapies that will improve outcomes in both humans and pet dogs with gliomas.

01 Jun 2016·Human Gene Therapy Clinical DevelopmentQ3 · MEDICINE

Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Patients with Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma

Q3 · MEDICINE

Article

Author: Gillespie, G. Yancey ; Foreman, Paul M. ; Nabors, L. Burt ; Riley, Kristen O. ; Patel, Daxa M. ; Markert, James M.

M032 is a second-generation oncolytic herpes simplex virus (oHSV) that selectively replicates in tumor cells. M032 kills tumor cells directly through oncolytic replication and then proceeds to infect tumor cells in proximity, continuing the process of tumor destruction. In addition to this direct oncolytic activity, the virus carries a therapeutic payload-thus acting as a gene therapy vector-and causes the tumor cell to synthesize and secrete the immunity-stimulating protein interleukin-12 (IL-12) before cell death. (1) Human IL-12 is expressed and promotes an immune response against surviving tumor cells, increasing the antitumor effect of the therapy. IL-12 also produces an antiangiogenic effect, by interfering with the production of new tumor blood vessels necessary for tumor growth. Thus, M032 oHSV exerts antitumor effects through three distinct potential mechanisms. The virus has also been genetically engineered to minimize toxic effects for the patient. Preclinical animal models support the safety of intracranial inoculation with M032 in two relevant species (mouse and nonhuman primate). This clinical protocol outlines the dose-escalating phase I study for evaluation of M032 in patients with recurrent or progressive malignant glioma.

100 Deals associated with NSC-733972

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma Multiforme	Phase 2	US	The University of Alabama at Birmingham	25 Feb 2022
Gliosarcoma	Phase 2	US	The University of Alabama at Birmingham	25 Feb 2022
Recurrent Malignant Glioma	Phase 1	US	The University of Alabama at Birmingham	25 Nov 2013