Clinical Trials

Date: 2017-02-13

Type of information: Treatment of the first patient

phase: 1

Announcement: treatment of the first patient

Company: Transgene (France) Centre Leon Berard (France)

Product: Pexa-Vec (pexastimogene devacirepvec)

Action mechanism:

oncolytic virus/gene therapy/oncolytic immunotherapy/monoclonal antibody/immune checkpoint inhibitor.
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. 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).
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation.
The combination of Pexa-Vec and ipilimumab aims at targeting two distinct steps in the immune response against cancer cells and is expected to be significantly more effective than either product alone.

Disease: metastatic and/or locally advanced solid tumors

Therapeutic area: Cancer - Oncology

Country: France

Trial details:

The ISI-JX trial is a phase 1 dose escalation trial evaluating the impact of an in situ immunization strategy with intra-tumoral injections of Pexa-Vec in combination with ipilimumab in metastatic / advanced solid tumors with injectable lesions. (NCT02977156)

Latest news:

• On February 13, 2017, Transgene announced that the first patient in the ISI-JX trial has been treated at the Léon Bérard Cancer Center in Lyon, France. ISI-JX is a Phase 1 clinical trial evaluating the intra-tumoral co-administration of Pexa-Vec in combination with ipilimumab in solid tumors. This investigator initiated trial promoted by the Leon Bérard Cancer Center will enroll patients with metastatic and/or locally advanced solid tumors. The trial will recruit up to 60 patients in several clinical centers in France. First readouts could be expected towards the end of 2017. The trial will evaluate the safety of the combination and evaluate the first signals for efficacy.