MUNICH— ORYX GmbH & Co. KG, a translational medicine company focused on oncolytic virotherapy and cancer vaccines, has published positive clinical trial results from a dose-escalating Phase 1/2a trial with oncolytic virus ParvOryx in metastatic, inoperable pancreatic cancer.
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 doesn’t affect normal cells and isn’t 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. Viral oncolysis induces a strong tumor-specific immune response leading to the recognition and elimination of minimal residual disease in animal models. In a previous Phase 1/2a trial with 18 patients with primary or recurrent glioblastoma, ParvOryx also showed changes in the tumor microenvironment and induction of specific immune responses.
ParvOryx was evaluated in an open label study in seven patients with metastatic, inoperable pancreatic cancer. The patients received ParvOryx at three increasing dose levels, partly administered intravenously on four consecutive days, followed by an intrametastatic injection into a single liver metastasis after 6 to 13 days. After virotherapy, patients were treated with gemcitabine. Primary endpoint of the trial evaluated safety and tolerability of ParvOryx.
Secondary endpoints included anti-tumor effects and cellular immune response, plus overall survival. To identify immunological and molecular signatures of responses, three serial liver biopsies (before, during, and after virotherapy) allowed for in-depth analyses of pathological tumor characteristics, tumor-infiltrating immune cells, quantification of cytokines and chemokines, and investigation of viral replication and tropism.
“We are pleased to present these positive data for ParvOryx, which confirm the promising results of previous trials with glioblastoma patients,” said Dr. Dr. Michael Dahm, CMO of ORYX. “With the successful completion of this trial, we have validated the mode of action of ParvOryx in another tumor type, inoperable metastatic pancreatic cancer, and have once more proven the excellent safety profile of the oncolytic virus. These clinical trial results are fully in line with our expectation that ParvOryx holds exceptional potential to treat a whole range of solid tumors.”
ParvOryx was safe at all dose levels and no maximum tolerated dose was reached. Two patients showed a partial response to virotherapy and prolonged overall survival times (326 and 555 days). These patients showed favorable immunological signatures, like changes in the tumor microenvironment and induction of specific immune responses.
Preliminary data were presented by Prof. Guy Ungerechts, principal investigator of the ParvOryx02 study, at the Oncolytic Virus Immunotherapy Summit in London in March. Final data were presented by Ungerechts at the International Oncolytic Virus Conference at the Mayo Clinic Center in Rochester this October.