M032 / The University of Alabama - LARVOL DELTA

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Sep 2025 ➔ Sep 2027

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • High Grade Glioma • Oncology • Sarcoma • Solid Tumor

Engineered HSV-1 M032 for the Treatment of Children and Adults With Newly Diagnosed Diffuse Midline Glioma After Standard of Care Radiation (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

A viral attack on brain tumors: the potential of oncolytic virus therapy. (PubMed, J Neurovirol) - "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."

Journal • Oncolytic virus • Review • Brain Cancer • Gene Therapies • Oncology • Solid Tumor

Study of Pembrolizumab and M032 (NSC 733972) (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Mar 2025 ➔ Mar 2028 | Trial primary completion date: Mar 2024 ➔ Mar 2027

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

Phase I clinical trial of oncolytic HSV-1 M032, a second-generation virus armed to expressed IL-12, for the treatment of adult patients with recurrent or progressive malignant glioma. (SNO 2023) - P1 | "Preliminary evidence suggests favorable response in some patients with recurrent or progressive MG. Careful selection of patients is needed when considering treatment with M032 (ClinicalTrials.gov number, NCT02062827)."

Clinical • P1 data • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IL12A

Study of Pembrolizumab and M032 (NSC 733972) (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: University of Alabama at Birmingham | Active, not recruiting ➔ Recruiting

Enrollment open • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Sep 2023 ➔ Sep 2024 | Trial primary completion date: Sep 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

Study of Pembrolizumab and M032 (NSC 733972) (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Recruiting ➔ Active, not recruiting | N=36 ➔ 24

Enrollment change • Enrollment closed • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor • MRI

A Phase I/II Study of Pembrolizumab and M032 (NSC 733972) (clinicaltrials.gov) - P1/2; N=28; Not yet recruiting; Sponsor: University of Alabama at Birmingham

Clinical • New P1/2 trial • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor • MRI

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: University of Alabama at Birmingham; Trial primary completion date: Sep 2021 ➔ Sep 2022

Clinical • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor • MRI

Oncolytic viruses as a promising therapeutic strategy against the detrimental health impacts of air pollution: The case of glioblastoma multiforme. (PubMed, Semin Cancer Biol) - "Engineered adenoviruses (i.e., DNX-2401, DNX-2440, CRAd8-S-pk7 loaded Neural stem cells), herpes simplex virus type 1 (i.e., HSV-1 C134, HSV-1 rQNestin34.5v.2, HSV-1 G207, HSV-1 M032), measles virus (i.e., MV-CEA), parvovirus (i.e., ParvOryx), poliovirus (i.e., Poliovirus PVSRIPO), reovirus (i.e., pelareorep), moloney murine leukemia virus (i.e., Toca 511 vector), and vaccinia virus (i.e., vaccinia virus TG6002) as possible life-changing alleviations for GBM have been discussed. We believe that the article will significantly appeal to a broad readership of virologists, oncologists, neurologists, environmentalists, and those who work in the field of (bio)energy. Policymakers may also use it to establish better health policies and regulations about air pollution and (bio)fuels exploration, production, and consumption."

Clinical • Journal • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Hematological Malignancies • Herpes Simplex • Immunology • Infectious Disease • Inflammation • Leukemia • Oncology • Solid Tumor

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. (PubMed, Neurosurg Focus) - "In 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."

Clinical • Journal • Glioma • Herpes Simplex • Immunology • Oligodendroglioma • Oncology • Solid Tumor

The One Health Consortium: Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Combination With a Checkpoint Inhibitor in Canine Patients With Sporadic High Grade Gliomas. (PubMed, Front Surg) - "The trial will evaluate M032, an Interleukin-12 expressing Herpes Simplex virus, alone and combined with a checkpoint inhibitor, Indoximod. The ability to compare human and dog responses in real time affords the most stringent test of suitability of the dog as an informative model of human brain tumors. Subsequent studies will allow canine trials to properly inform the design of human trials."

Checkpoint inhibition • Clinical • Combination therapy • Journal • P1 data • Glioma • Herpes Simplex • Oncology • Solid Tumor

[VIRTUAL] The One Health Consortium and combination immunotherapy: evaluating M032, a genetically engineered HSV-1 expressing Il-12, in combination with a checkpoint inhibitor in canine glioma patients (AACR-II 2020) - "The trial is evaluating M032, an Interleukin-12 expressing Herpes Simplex virus, alone and combined with a checkpoint inhibitor, Indoximod. The ability to compare human and dog responses in real time affords the most stringent test of suitability of the dog as a valid and informative model of human brain tumors. The results of this and subsequent studies will allow canine trials to properly inform the design of human trials and further support bi-translational studies and the One Medicine approach to clinical research and application."

Checkpoint inhibition • Clinical • Combination therapy • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IL12A

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: University of Alabama at Birmingham; Trial completion date: Sep 2022 ➔ Sep 2023; Trial primary completion date: Sep 2020 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date

Phase I immunovirotherapy trial of IL-12 expressing HSV-1 (M032) in pet dogs with spontaneous high grade gliomas: a preliminary report (SNO 2019) - "We describe a prospective, phase I clinical trial in canine patients with sporadic high-grade gliomas to evaluate M032, a mutant HSV-1 expressing IL-12, alone or combined with a checkpoint inhibitor (Indoximod) to assess safety, tolerability and efficacy. This same virus is being tested in a phase 1 clinical trial in humans with high-grade malignant gliomas; eight human patients have received treatment at this writing without virus-related toxicities. The concurrent prosecution of both trials allows unprecedented real time comparison of safety and efficacy of immunovirotherapy as a stringent test of suitability of the dog as a valid and informative model of human brain tumors."

P1 data • IL12A

Enhanced Sensitivity of Patient-Derived Pediatric High-Grade Brain Tumor Xenografts to Oncolytic HSV-1 Virotherapy Correlates with Nectin-1 Expression. (PubMed, Sci Rep) - "Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively...Treatment with oHSV resulted in prolonged survival in both pediatric and adult intracranial patient-dervied tumor xenograft models. Our results suggest that pediatric brain tumors are ideal targets for oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to predict patient response to oHSV."

Biomarker • Clinical • Journal • Oncolytic Virus

One-Health tumor model and preliminary report of a phase 1 immunovirotherapy trial of IL-12 expressing HSV-1 (M032) in pet dogs with spontaneous high grade gliomas (SNO 2019) - No abstract available.

P1 data

M032-HSV-1: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: University of Alabama at Birmingham; Trial completion date: Sep 2020 ➔ Sep 2022; Trial primary completion date: Sep 2019 ➔ Sep 2020

Clinical • Trial completion date • Trial primary completion date