Date: 2017-07-31
Type of
information: Treatment of the first patient
phase: 1-2
Announcement: treatment of the first patient
Company: Transgene (France)
Product: Pexa-Vec (pexastimogene devacirepvec) with Opdivo®(nivolumab)
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, 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).
- Opdivo® (Nivolumab) is a fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. PD-1, a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. Opdivo® is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them.
- Opdivo® is the world’s first approved drug targeting PD-1. This antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex. When Medarex was acquired by BMS in 2009, it also granted BMS its rights to develop and commercialize the anti-human PD-1 monoclonal antibody in North America. Through the collaboration agreement entered into in September 2011 between Ono and BMS, Ono granted BMS exclusive rights to develop and commercialize Opdivo® in the rest of the world, except in Japan, Korea and Taiwan where Ono has retained all rights to develop and commercialize the compound.
Disease: advanced hepatocellular carcinoma
Therapeutic
area: Cancer - Oncology
Country: France
Trial
details:
- This phase I/IIa trial will evaluate the safety and efficacy of the combination of the oncolytic immunotherapy Pexa-Vec with the PD-1 receptor blocking antibody nivolumab in the first-line treatment of advanced hepatocellular carcinoma. (NCT03071094)
Latest
news:
- • On July 31, 2017, Transgene announced that the first patient has been treated in a Phase 1/2 clinical trial evaluating the combination of Pexa-Vec with Opdivo® (nivolumab) as a first-line treatment of advanced hepatocellular carcinoma. This open-label trial will assess the safety and tolerability as well as the anti-tumor activity and efficacy of this immunotherapy combination regimen in up to 36 patients. The principal investigator of this multi-center trial is Prof Olivier Rosmorduc, Head of Hepato-gastroenterology department at La Pitié-Salpêtrière Hospital in Paris.
- In a Phase 2 trial of Pexa-Vec in first-line hepatocellular carcinoma, overall survival was improved in a dose dependent manner. The median overall survival was 14.1 months for the high-dose group compared to 6.7 months for the low-dose group.
Is
general: Yes
