Date: 2013-09-03
Type of
information: Results
phase: 2b
Announcement: results
Company: Transgene (France) Jennerex (USA)
Product: JX-594/TG6006 (Pexa-Vec -pexastimogene devacirepvec)
Action
mechanism:
- oncolytic virus/gene therapy/oncolytic immunotherapy. Pexa-Vec (pexastimogene devacirepvec) is an oncolytic immunotherapy that utilizes the vaccinia poxvirus strain as its backbone. This strain has been used safely in millions of people as part of a worldwide vaccination program. 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, i.e., active immunotherapy.
Disease: hepatocellular carcinoma
Therapeutic
area: Cancer Oncology
Country: North America, South Korea, Taiwan, Hong Kong, and Europe
Trial
details:
- The TRAVERSE Phase IIb clinical trial enrolled 120 patients and is being conducted at approximately 40 sites in North America, South Korea, Taiwan, Hong Kong, and Europe. The primary objective of the trial is to determine the overall survival benefit for patients receiving JX594/TG6006 with best supportive care, compared to best supportive care alone in patients with refractory advanced liver cancer.
Latest
news:
- • On September 3, 2013, Transgene has announced that TRAVERSE, a randomized Phase 2b study of Pexa-Vec in second-line, advanced liver cancer patients had reached the pre-specified number of events for analysis. The study failed to meet its primary endpoint of overall survival for Pexa-Vec plus best supportive care (BSC) compared to BSC. Pexa-Vec was generally well tolerated with an adverse event profile consistent with previous Pexa-Vec studies in patients with advanced HCC. Additional analyses will be conducted to further understand these data. The decision to move Pexa-Vec into Phase 3 in first line HCC next year is still expected to be made in Q4 2013. Besides the TRAVERSE trial, Pexa-Vec is currently being evaluated in kidney, colorectal, and ovarian cancers through 4 other ongoing clinical studies.
- • On May 21, 2013, Transgene has announced completion of enrollment in the 120-patient TRAVERSE study. This study is a global randomized phase 2b clinical trial evaluating the efficacy and safety of Pexa-Vec (JX-594/TG6006, pexastimogene devacirepvec) for the treatment of advanced primary liver cancer (hepatocellular carcinoma, HCC) in patients who failed prior therapy with sorafenib (Nexavar®). The primary objective of TRAVERSE is to determine the overall survival for patients receiving Pexa-Vec with best supportive care, compared to those receiving best supportive care alone.
- Data from a previous phase 2 clinical trial using Pexa-Vec to treat liver cancer was recently published in Volume 19, Issue 2 of Nature Medicine in February of 2013. In this study, thirty patients were randomized into the low and high dose groups and received three Pexa-Vec treatments over the course of four weeks. The results demonstrated that Pexa-Vec was able to significantly prolong overall survival with 14.1 months median survival for the high-dose group compared to 6.7 months for the low-dose group (p-value = 0.02). The data further demonstrated that Pexa-Vec treatment at both doses resulted in a reduction in tumor size and decreased blood flow in tumors. Induction of an immune response against the tumor, evidenced by antibody-mediated tumor cell toxicity, was also observed. Pexa-Vec was well-tolerated at both high and low doses with the most frequent adverse events consisting of flu-like symptoms lasting less than 24 hours. This was the first randomized clinical trial of an oncolytic immunotherapy demonstrating significantly prolonged overall survival.
- In addition to TRAVERSE, Pexa-Vec is currently being evaluated as monotherapy in sorafenib-naïve HCC patients and in combination with sorafenib. Pexa-Vec is also being evaluated in a phase 1/2 clinical trial in patients with treatment-refractory colorectal cancer as monotherapy and in combination with irinotecan, and in a Phase 2a clinical trial in treatment-refractory kidney cancer patients.
- • On November 4, 2011, Transgene and Jennerex have announced that enrollment has been initiated and the first patient has been randomized in a Phase IIb clinical trial called TRAVERSE. The trial is evaluating the use of JX594/TG6006 to treat patients with advanced liver cancer, also known as hepatocellular carcinoma (HCC), who failed prior therapy with Nexavar® (sorafenib), the only approved drug for HCC. The randomization of the first patient in the TRAVERSE study triggers an undisclosed milestone payment from Transgene to Jennerex. The TRAVERSE study should recruit 120 patients in 45 sites globally.
Is
general: Yes
