Transgene, a company that designs and develops viral-based immunotherapies,  announced that the first patient with soft tissue sarcoma (STS) has been treated in the phase 2 of the METROmaJX clinical trial at Institut Bergonié (Bordeaux, France). METROmaJX is a phase 1/2 clinical trial evaluating the tolerability and efficacy of the co-administration of Pexa-Vec with metronomic cyclophosphamide (low doses given with high frequency) in patients with advanced solid tumors such as breast cancer and STS (NCT02630368).

In Phase 1 of the trial, the combination of Pexa-Vec and low-dose cyclophosphamide demonstrated a satisfactory tolerability profile, allowing the trial to progress to the phase 2. The results of the Phase 1 of the study will be presented at upcoming scientific congresses.

The phase 2 stage of this open-label trial will enroll patients with soft tissue sarcoma (STS) and HER2 negative-breast cancer. It will primarily assess the anti-tumor efficacy of this novel combination regimen. This investigator-initiated trial is supported by INCa (French National Cancer Institute) within the frame of the CLIP projects.

Pexa-Vec is a GM-CSF expressing vaccinia derived oncolytic virus co-developed by Transgene and SillaJen. Cyclophosphamide is a chemotherapy. Metronomic administration involves giving low doses of the drug at a higher frequency and is known to have an immunomodulating activity.

Pr Antoine Italiano, MD, PhD, from Institut Bergonié, an expert in early phase research and principal investigator of the study, said: “The METROmaJX trial has confirmed the good tolerability of intravenous administration of the oncolytic virus Pexa-Vec, when associated with low-dose cyclophosphamide. We hope this novel regimen will demonstrate its efficacy in the phase 2 part of the trial.”

The combination of Pexa-Vec and cyclophosphamide aims at targeting two distinct steps in the immune response against cancer cells and has the potential to be significantly more effective than either product alone. Pexa-Vec is an oncolytic virus designed to selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells via viral replication,  reduce the blood supply to tumors through vascular disruption, and stimulate the body’s immune response against cancer cells. Pexa-Vec’s mechanism of action and its safety profile make it an appropriate candidate for combinations with other immunomodulating therapies to potentially improve its anti-cancer effects.

Maud Brandely, chief medical officer of Transgene, said: “We are grateful to Institut Bergonié and INCa for supporting the METROmaJX trial. We hope that the phase 2 part of the study will demonstrate that this novel oncolytic virus plus chemotherapy regimen can be synergistic resulting in a high response rate which could translate into improved overall survival. Advanced breast cancer and soft tissue sarcoma are two diseases which clearly require better treatment options for the patients.”