Clinical Trials

Date: 2017-07-21

Type of information: update on patient enrollment

phase: 3

Announcement: update on patient enrollment

Company: Transgene (France) Sillajen (Republic of Korea)

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,(active immunotherapy).

Disease: hepatocellular carcinoma (HCC)

Therapeutic area: Cancer - Oncology

Country: Australia, Canada, China, France, Germany, Hong Kong, Israel, Italy, Republic of, Korea, New Zealand, Portugal, Singapore, Taiwan, Thailand, UK, USA

Trial details:

• PHOCUS is a randomized Phase 3 study to determine whether treatment with vaccinia virus based immunotherapy (Pexa-Vec) followed by sorafenib increases survival compared to treatment with sorafenib in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy. It is designed to enroll 600 patients who have not received prior systemic treatment for their cancer, and they will be randomized to one of two treatment groups: one which will receive Pexa-Vec followed by sorafenib and one which will receive sorafenib alone.
• The randomized study will be conducted at approximately 140 sites worldwide. The primary objective of the study is to determine the overall survival of patients treated with Pexa-Vec. Secondary objectives include safety as well as assessments for tumor responses between the two groups as measured by the following endpoints: time to progression, progression-free survival, overall response rate and disease control rate. (NCT02562755)

Latest news:

• • On July 21, 2017, SillaJen and Lee's Pharmaceutical, a research based biopharmaceutical company, announced approval (Approval No. 2017L04441) by the China Food and Drug Administration (CFDA) to conduct a Phase 3 clinical trial for advanced liver cancer using its oncolytic immunotherapy called Pexa-Vec (formerly JX-594), the PHOCUS study.
• • On April 24, 2017,  SillaJen and Transgene have enrolled the first European patient in the ongoing multinational randomized Phase 3 open-label study of Pexa-Vec (formerly JX-594), in patients with advanced hepatocellular carcinoma. The trial is evaluating the use of Pexa-Vec to treat HCC patients who have failed locoregional therapies and are eligible for treatment with sorafenib (Nexavar®), the only approved systemic treatment for advanced HCC. The European patient was enrolled at Azienda Ospedaliero-Universitaria Hospital in Parma, Italy. The study, named the PHOCUS trial,  is now active in North America, Asia, Australia and Europe. The enrollment of the first European patient triggers a $4 million milestone to be paid to SillaJen by Transgene.
• • On January 6, 2016, Transgene announced the initiation of the PHOCUS trial. This multinational, randomized Phase 3 open label study is being led by Transgene’s partner, SillaJen. The trial is evaluating the oncolytic immunotherapy, Pexa-Vec, in patients with hepatocellular carcinoma (HCC) who are eligible for treatment with sorafenib (Nexavar®), the only approved drug for advanced HCC. The study is designed to enroll 600 patients who have not received prior systemic treatment for their cancer. Patients will be randomized 1:1 to one of two treatment groups: one which will receive Pexa-Vec followed by sorafenib and one which will receive sorafenib alone. The study will be conducted at approximately 140 sites worldwide, including in North America, Asia, Australia and Europe. SillaJen reached agreement with the FDA on a Special Protocol Assessment (SPA) for this global Phase 3 clinical trial. The primary endpoint of the study will be overall survival. Secondary objectives will include safety, as well as assessments for tumor responses between the two groups as measured by the following endpoints: time to progression, progression-free survival, overall response rate and disease control rate.
• • On November 12, 2015, Transgene and SillaJen announced that they have signed an amended agreement for the development and commercialization of oncolytic viral therapy Pexa-Vec to streamline the conduct of clinical trials and to reflect important areas of interest for each company. On this occasion, the companies also outlined key parts of the current clinical development plan for Pexa-Vec. Phase 3 trial in HCC expected to initiate soon. The Phase 3 trial of Pexa-Vec, named PHOCUS, followed by sorafenib in the first-line treatment of patients with advanced hepatocellular carcinoma, is on track to initiate in the fourth quarter of this year.  The trial is being led by SillaJen and is planned to enroll approximately 600 patients in North America, Europe and Asia. The study is being conducted under a Special Protocol Assessment (SPA) with the FDA.
• Transgene is independently conducting several exploratory studies with Pexa-Vec. Two trials in combination with immune checkpoint inhibitors are being planned and are expected to initiate during 2016: a study with nivolumab in advanced HCC and another with ipilimumab in advanced melanoma. Two other studies are underway and patients have been dosed: 1) a study evaluating Pexa-Vec in combination with metronomic cyclophosphamide, a drug used in combination with other therapies to treat a wide variety of cancers, mainly in patients with advanced breast cancer or soft tissue sarcoma, is being sponsored by the Bergonié Institute (Bordeaux, France); and 2) a study evaluating Pexa-Vec in cancer patients in the pre-surgery (neoadjuvant) setting to further document the mechanism of action of Pexa-Vec is being sponsored by the University of Leeds (Leeds, United Kingdom).
• • On April 16, 2015, Transgene reported that an agreement has been reached with the FDA on a Special Protocol Assessment (SPA) for the global Phase 3 clinical trial of the oncolytic immunotherapy, Pexa-Vec. The SPA now enables Transgene, SillaJen, Inc. and the other global partners for Pexa-Vec to have clarity on the acceptability of the global Phase 3 study. The pivotal trial will evaluate the use of Pexa-Vec to treat patients with advanced liver cancer, also known as hepatocellular carcinoma (HCC), who have not received sorafenib (Nexavar®) therapy and is expected to begin enrollment later this year. The Phase 3 clinical trial is designed to enroll 600 patients with advanced liver cancer who are eligible to receive sorafenib therapy. The randomized study will be conducted at approximately 120 sites worldwide including North America, Asia, and Europe. The primary objective of the trial is to determine the overall survival benefit for patients receiving PexaVec followed by sorafenib, compared to sorafenib alone in patients with advanced liver cancer.

Is general: Yes