Clinical Trials

Date: 2017-07-07

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2017 Congress

Company: Institut Bergonié (France) Transgene (France)

Product: JX-594/TG6006 (Pexa-Vec -pexastimogene devacirepvec) and cyclophosphamide

Action mechanism:

oncolytic virus/gene therapy/oncolytic immunotherapy/antineoplastic agent. Pexa-Vec (pexastimogene devacirepvec) is an oncolytic immunotherapy that utilizes the vaccinia poxvirus strain as its backbone. This strain naturally targets cancer cells due to common genetic defects in cancer cells; Pexa-Vec was engineered to enhance this by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack.
Pexa-Vec is designed to attack cancer through three diverse mechanisms of action:
1) the lysis of cancer cells through viral replication,
2) the shutdown of the blood supply to tumors through vascular targeting and destruction, and
3) the stimulation of the body's immune response against cancer cells,(active immunotherapy).
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.

Disease: soft tissue sarcoma (STS), HER2 negative-breast cancer

Therapeutic area: Cancer - Oncology

Country: France

Trial details:

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 tumours.
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.
Prof. Antoine Italiano is the principal investigator of the trial. Institut Bergonié is the sponsor of this trial, that is supported by INCa (French National Cancer Institute) within the frame of the CLIP² projects. (NCT02630368).

Latest news:

• On September 11, 2017, Transgene has presented results of the Phase 1 part of the METROmaJX trial at the annual congress of European Society for Medical Oncology (ESMO) (8-12 September 2017, Madrid, Spain). These Phase 1 trial results showed that the regimen associating intravenous infusion of Pexa-Vec (JX-594) with low-dose cyclophosphamide was well-tolerated with no dose limiting toxicity in patients with solid tumours. (Abstract title: A phase Ib trial of JX-594 (Pexa-Vec), a targeted multimechanistic oncolytic vaccinia virus, in combination with low-dose cyclophosphamide in patients with advanced solid tumours -Poster number: 414P)
Following these positive results, the Phase 2 part of the trial is currently enrolling patients with soft tissue sarcoma (STS) and HER2 negative-breast cancer. It will primarily assess the anti-tumour efficacy of this novel combination regimen.
• On April 12, 2017, Transgene announced that the first patient with soft tissue sarcoma (STS) has been treated in the Phase 2 part of the METROmaJX clinical trial at Institut Bergonié (Bordeaux, France). In the Phase 1 part 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 part.