Parvovirus H1 – ParvOryx

 

Description

ParvOryx is an oncolytic parvovirus H1 (H-1PV), a wild type rat virus that infects and lyses tumor cells from a wide variety of cancers. These tumor types include 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 = small) is the smallest of all oncolytic viruses and is able to cross the blood brain barrier. Unlike other natural or modified oncolytic viruses currently under investigation, ParvOryx does not affect normal cells and is not pathogenic to humans.

The special properties of ParvOryx allow for both intratumoral and intravenous administration as well as repeated application (booster).

Mode of Action

H-1PV acts at relatively low multiplicities of infection. The virus exerts both cytotoxic and oncolytic (replication) effects. The cytotoxic effect is predominantly mediated by the non-structural protein (NS1), resulting in cell transcription dysregulation, cell cycle arrest, cell replication shut off, 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).

Clinical Evidence of Efficacy

ParvOryx has successfully completed a Phase I/IIa trial to treat glioblastoma multiforme in 18 patients with recurrent or progressive disease. A dose-escalating Phase I/IIa pilot study for the treatment of metastatic pancreatic cancer with ParvOryx monotherapy is currently ongoing, with topline data expected in Q4 2017. In addition, ParvOryx is currently studied in compassionate uses in combination with immune-oncology drugs such as Avastin® (bevacizumab) and various immune checkpoint inhibitors.

Data from the two Phase I/IIa trials together with data from the combination of ParvOryx with Avastin® and/or immune checkpoint inhibitors indicate that ParvOryx is able to turn an immunogenic “cold” into a “hot” tumor by profoundly changing its microenvironment. This virus-induced change to the tumor microenvironment makes the tumor vulnerable against many immuno-oncology approaches, which, based on preliminary clinical findings, appears to improve progression-free-survival (PFS) and overall survival (OS).

ParvOryx 01 Trial in Glioblastoma Multiforme

A Phase I/IIa trial in patients with primary or recurrent glioblastoma multiforme using parvovirus H1 has been successfully completed.

Primary objectives of the prospective open-label, single-center dose-escalation trial were safety, maximum tolerated dose, viremia (presence of virus in the blood) and viral shedding.

Secondary objectives were progression-free survival and overall survival.

Results: ParvOryx clearly demonstrated that it was safe and induced both strong tumor infiltration patterns and cellular immune responses against glioma and viral proteins (bystander effect). Overall survival for the majority of patients (77.8%) was at least six months, some of them significantly longer (40.9 months).

Results were presented at several congresses (e.g., ASCO) with throughout positive response. A paper describing the results of the trial was recently submitted for publication.

ParvOryx 02 Pilot Study in Pancreatic Cancer

A dose-escalation Phase I/IIa pilot study with ParvOryx in patients with metastatic, inoperable pancreatic cancer was initiated in the second quarter of 2016. The prospective, single-center open-label trial includes patients with at least one hepatic metastasis.

The primary endpoint of this study are safety, humoral immune response, pharmacokinetic examination and viral shedding.

Secondary endpoints include anti-tumor effects and cellular immune response, as well as progression-free survival and overall survival.

Topline results are expected in Q4 2017.

For more information see: ClinicalTrials.gov