HSV G207 / UAB University - Birmingham, Treovir - LARVOL DELTA

HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma (clinicaltrials.gov) - P2 | N=35 | Suspended | Sponsor: Pediatric Brain Tumor Consortium | Recruiting ➔ Suspended

Trial suspension • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Astrocytoma • Brain Cancer • CNS Disorders • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Feb 2029 ➔ Feb 2030 | Trial primary completion date: Dec 2028 ➔ Dec 2029

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor

Treovir and Matica Bio Forms Strategic Partnership to Advance Innovative Therapies for Pediatric Brain Tumors (Businesswire) - "Matica Biotechnology...announced a strategic partnerships with Treovir. The collaboration aims to advance innovative therapies for pediatric patients with brain and other neurological cancers. Matica Bio will provide GMP manufacturing for clinical supplies. Treovir, a biotechnology company developing oncolytic immunotherapies, will partner with Matica Bio on its G207 HSV-based oncolytic therapy for treating glioblastoma and other brain tumors in children."

Licensing / partnership • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Oncolytic HSV rewires metabolism to promote antitumor immunity through reductive carboxylation and ferroptosis (SNO 2024) - P1/2 | "RNA-seq data obtained from pre- and post-G207 treated biopsies from phase-Ib study patients (NCT00028158) revealed enrichment in pathways related to citric acid cycle, oxidative phosphorylation, and glutamate metabolism...IDH mutant tumors that block reductive carboxylation were resistant to oHSV-induced ferroptotic cell death and did not benefit from oHSV-induced antitumor benefit. Together, this study presents avenues to enhance antitumor immunity by oHSV therapy."

IO biomarker • Brain Cancer • CNS Tumor • Glioma • Herpes Simplex • Malignant Glioma • Melanoma • Oncology • Solid Tumor

HSV G207 with a Single Radiation Dose in Children with Recurrent High-Grade Glioma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Pediatric Brain Tumor Consortium | Not yet recruiting ➔ Recruiting

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

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Gregory K. Friedman, MD | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Astrocytoma • Brain Cancer • CNS Disorders • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Gregory K. Friedman, MD | Recruiting ➔ Active, not recruiting | N=15 ➔ 24

Enrollment change • Enrollment closed • Astrocytoma • Brain Cancer • CNS Disorders • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Gregory K. Friedman, MD | Active, not recruiting ➔ Completed

Trial completion • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Oncology • Solid Tumor

The safety and accuracy of intratumoral catheter placement to infuse viral immunotherapies in children with malignant brain tumors: a multi-institutional study. (PubMed, J Neurosurg Pediatr) - P1, P1b | "Although instances of minor hemorrhage were encountered, they were clinically asymptomatic. One of 49 catheters required intervention for a CSF leak. Congruent with previous studies in the literature, the stereotactic placement of catheters in these pediatric tumor patients was accurate with approximately 95% of catheters having been adequately placed."

Clinical • Journal • Brain Cancer • CNS Tumor • Glioma • Hematological Disorders • Infectious Disease • Oncology • Pediatrics • Solid Tumor

Elucidating cellular response to treatment with viral immunotherapies in pediatric high-grade glioma and medulloblastoma. (PubMed, Transl Oncol) - "RNA sequencing of control cells and cells treated for 8 and 24 h revealed that there were few shared differentially expressed (DE) genes between cells treated with PVSRIPO and G207: GCLM, LANCL2, and RBM3 were enriched whilst ADAMTS1 and VEGFA were depleted. Likewise, there were few shared DE genes enriched between medulloblastoma and high-grade glioma cell lines treated with G207: GPSM2, CHECK2, SEPTIN2, EIF4G2, GCLM, GDAP1, LANCL2, and PWP1.  Treatment with G207 and PVSRIPO appear to cause disparate gene enrichment and depletion suggesting disparate molecular mechanisms in malignant pediatric brain tumors."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Infectious Disease • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • ADAMTS1 • LANCL2 • NECTIN1 • PVR

HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Oncolytic virotherapies for pediatric tumors. (PubMed, Expert Opin Biol Ther) - "We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future."

Journal • Oncolytic virus • Review • Herpes Simplex • Infectious Disease • Measles • Oncology • Pediatrics • Solid Tumor

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Gregory K. Friedman, MD | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Astrocytoma • Brain Cancer • CNS Disorders • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Apr 2028 ➔ Nov 2028 | Trial primary completion date: Apr 2028 ➔ Nov 2028

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

HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Dec 2022 ➔ Jan 2024

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Oncology • Solid Tumor

Intraventricular immunovirotherapy; a translational step forward. (PubMed, Oncotarget) - "A recent preclinical study has paved the way for clinical translation of intraventricular administration of oHSV by identifying and mitigating the toxicity associated with this route for therapeutic benefit in murine models of disseminated medulloblastoma. This work may ultimately allow for targeting of intractable disease and provides a feasible option for the repetitive dosing of clinically relevant immunovirotherapy, G207."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Glioma • Herpes Simplex • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies (ASH 2021) - P2 | "The phase 2 randomized GRIFFIN study (NCT02874742) evaluates frontline DARA in combination with lenalidomide, bortezomib, and dexamethasone (D-RVd) in transplant-eligible NDMM...The phase 2 MASTER study (NCT03224507) evaluates DARA plus carfilzomib, lenalidomide, and dexamethasone (D-KRd) in transplant-eligible NDMM (Costa LJ, et al... In GRIFFIN, among 207 (D-RVd, n=104; RVd, n=103) randomized pts, 91.3% (n=95) of D-RVd pts and 77.7% (n=80) of RVd pts underwent stem cell mobilization; of those mobilized, 98.9% (n=94) and 97.5% (n=78) underwent ASCT, respectively... The addition of DARA to proteasome inhibitor/immunomodulatory drug/dexamethasone-based induction therapy has a modest impact on stem cell mobilization, with a lower yield of stem cells and higher median number of days required for collection. Nonetheless, pts were able to undergo transplantation, and most pts collected sufficient stem cells for 2 transplants. Pts who received plerixafor by an upfront..."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • Transplantation • CD34 • CXCR4

Safety and efficacy of intraventricular immunovirotherapy with oncolytic HSV-1 for CNS cancers. (PubMed, Clin Cancer Res) - "Toxicity from intraventricular oHSV can be mitigated resulting in therapeutic benefit. These data support clinical translation of intraventricular G207."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Herpes Simplex • Oncology • Pediatrics • Solid Tumor • CD8

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Astrocytoma • Brain Cancer • CNS Disorders • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Jun 2022 ➔ Dec 2022

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Oncology • Solid Tumor

HSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Immunology • Oncology • Solid Tumor

Clinical advances in oncolytic virotherapy for pediatric brain tumors. (PubMed, Pharmacol Ther) - "While the majority of brain tumor clinical trials utilizing oncolytic virotherapy have been in adults, five viruses are being tested in pediatric brain tumor clinical trials: herpes simplex virus (G207), reovirus (pelareorep/Reolysin), measles virus (MV-NIS), poliovirus (PVSRIPO), and adenovirus (DNX-2401, AloCELYVIR). Herein, we review past and current pediatric immunovirotherapy brain tumor trials including the relevant preclinical and clinical research that contributed to their development. We describe mechanisms by which the viruses may overcome barriers in treating pediatric brain tumors, examine challenges associated with achieving effective, durable responses, highlight unique aspects and successes of the trials, and discuss future directions of immunovirotherapy research for the treatment of pediatric brain tumors."

Journal • Oncolytic virus • Review • Brain Cancer • Glioma • Hematological Disorders • Hematological Malignancies • Herpes Simplex • Infectious Disease • Oncology • Pediatrics • Solid Tumor

Chromogenic In Situ Hybridization for High Risk Human Papillomavirus RNA in Fine Needle Aspiration Samples of Metastatic Oropharyngeal Squamous Cell Carcinoma (USCAP 2022) - " 60 FNAs positive for metastatic OPSCC were identified among 207 neck FNA reports, of which 39 (65%) corresponded to HPV-OPSCC, 14 (23.3%) to HPV-negative OPSCC, and 8 (13.3%) were OPSCC with unknown HPV status... HR-HPV RNA ISH is an HPV-specific test that does not require a cut-off and is interpreted as positive or negative. While current guidelines recommend p16 immunohistochemistry as the best initial test in surgical specimens, several studies have debated reliability of p16 staining in cytology, mainly for two reasons: 1) many samples are cystic and yield low cellularity, and 2) it has been difficult to establish a reproducible p16 positivity cut-off. Application of HPV-specific methods in cytology may return cost and time-efficient benefits in diagnosis and management of OPSCC and CUP."

Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study. (PubMed, Clin Cancer Res) - "Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV."

Journal • Oncolytic virus • P1 data • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • Oncology • Solid Tumor