ORYX: Positive data from Phase I/IIa clinical trial in glioblastoma with oncolytic virus ParvOryx published in peer-reviewed journal, Molecular Therapy
- Category: DNA RNA and Cells
- Published on Monday, 06 November 2017 11:29
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MUNICH, Germany I November 06, 2017 I ORYX, a translational medicine company focused on oncolytic virotherapy and cancer vaccines, today announced that positive clinical data from a first-in-humans Phase I/IIa trial in glioblastoma with the oncolytic virus, ParvOryx, will be published in the peer-reviewed medical journal, Molecular Therapy. The article "Oncolytic H-1 parvovirus shows safety and signs of immunogenic activity in a first phase I/II glioblastoma trial," is scheduled to appear in the Volume 25 (Issue 12) of Molecular Therapy and can already be accessed online. The lead co-authors are Dr. Karsten Geletneky, Dr. Jacek Hajda, Prof. Dr. Andreas Unterberg and Prof. Dr. Jean Rommelaere.
The Phase I/IIa study was an open-label, dose escalation, single-center study. Eighteen patients with recurrent glioblastoma were treated with ParvOryx via intratumoral or intravenous injection. Tumors were resected nine days after treatment, and ParvOryx was re-injected around the resection cavity. Primary endpoints were safety and tolerability, virus distribution and maximum tolerated dose (MTD). Progression-free and overall survival, as well as levels of viral and immunological markers in the tumor and peripheral blood, were also assessed.
In the trial, ParvOryx treatment was safe and well tolerated, and an MTD was not reached. No dose-dependent side effects or dose-limiting toxicities were observed. The virus was able to cross the blood-brain/tumor barrier and spread widely through the tumor. ParvOryx was shown to have a favorable, predictable pharmacokinetic profile, induced antibody formation in a dose-dependent manner and triggered specific T-cell responses in the peripheral blood. Markers of viral replication, microglia/macrophage activation, and cytotoxic T-cell infiltration were detected in infected tumors, suggesting that ParvOryx may trigger an immune response. Clinical response was independent of the mode of ParvOryx administration. Albeit from a small, heterogenous patient group, progression-free survival of 15.9 weeks and overall survival of 464 days compared favorably with published data of meta-analyses in recurrent glioblastoma patients and were in the range of recently reported positive results from a trial using a replication-competent armed retrovirus.
"These published data provide good insight into the safety and mode of action of the oncolytic virus ParvOryx in glioblastoma, an aggressive and difficult-to-treat cancer," commented Prof. Dr. Jean Rommelaere, Head of Tumor Virology, German Cancer Research Center. "The clinical and scientific evidence obtained from this pilot study supports further developing ParvOryx in this indication, as well as other tumor types, and we look forward to initiating additional studies with this novel oncolytic virus, including in combination with immune activators."
The Molecular Therapy journal is published by the American Society of Gene and Cell Therapy (ASGCT) and focuses on research on the development of molecular and cellular therapeutics.
ParvOryx (Parvovirus H1) is a wild type rat oncolytic virus that infects and lyses tumor cells in a wide variety of cancers, including glioblastoma multiforme, pancreatic cancer, breast cancer, lung cancer, melanoma, lymphoma, pediatric tumors such as neuroblastoma and medulloblastoma, prostate cancer and renal cancer, as well as tumor stem cells. ParvOryx (parvus, the smallest among all oncolytic viruses), is able to cross the blood brain barrier. The special properties of ParvOryx allow for both intratumoral and intravenous administration as well as repeated application. H-1PV does not affect normal cells and is not pathogenic for humans. The virus exerts a cytotoxic/oncolytic effect, resulting in dysregulation of cell transcription, cell cycle arrest, shut off of cell replication, activation of cellular stress response and induction of cell death. In addition, viral oncolysis induces a strong tumor-specific immune response leading to the recognition and elimination of minimal residual disease (bystander effect) in animal models. ParvOryx can turn an immunogenic "cold" into a "hot" tumor by profoundly changing its microenvironment, making the tumor vulnerable to a variety of immuno-oncological approaches.
ParvOryx successfully completed a Phase I/IIa trial to treat glioblastoma multiforme in 18 patients with recurrent or progressive disease. A dose-escalation Phase I/IIa pilot study for the treatment of metastatic pancreatic cancer with ParvOryx monotherapy is currently ongoing, with topline data expected in the fourth quarter of 2017.
ORYX is a privately held Munich-based biotech company. ORYX is developing three highly innovative drug candidates for the treatment of cancer, originating from leading research institutions like the German Cancer Research Center (DKFZ) and the University of Heidelberg. The ORYX clinical development portfolio consists of an oncolytic virus and two therapeutic cancer vaccines. ORYX holds exclusive, worldwide licenses for all its development projects. For more information, please visit: www.oryx-medicine.com
 Source: Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. Sci Transl Med. 8, 341ra75 (2016).