Enrollment of Phase 3 study in first-line advanced liver cancer expected to begin by mid-2015 - To initiate several additional Phase 1/2 trials during 2014
Marchc 26, 2014
Transgene SA, Lee’s Pharmaceutical and SillaJen today unveiled their late-stage clinical development plan for Pexa-Vec oncolytic immunotherapy. The companies plan to initiate a global Phase 3 study in the first-line treatment of advanced hepatocellular carcinoma (HCC, liver cancer) patients, as well as several additional Phase 1/2 trials in different cancers, both as a single agent and in combination with a variety of other treatments, including immunotherapies such as immune checkpoint inhibitors. In addition, the partners plan to undertake several exploratory trials of intravenous infusion therapy in various tumor types, including renal, breast and soft tissue sarcoma.
Dr. Eun-Sang Moon, CEO of SillaJen, Inc. said: “With the recent closing of our acquisition of Jennerex, Inc., we are very excited to focus, together with Transgene and our other partners, on advancing and broadening the clinical development for Pexa-Vec, our innovative oncolytic immunotherapy. We believe that this emerging multi-mechanistic therapeutic class holds great promise in treating patients with cancers for which today there are very limited treatment options. In a dose-finding Phase 2 study, Pexa-Vec has demonstrated clinical activity with IV delivery. High-dose Pexa-Vec was associated with longer survival benefit in first-line liver cancer patients in Phase 2b, as published in Nature Medicine.”
Philippe Archinard, Chairman and Chief Executive Officer of Transgene, said: “Together with SillaJen and our other partners, we are pleased to be moving forward our joint development plan for Pexa-Vec. Pexa-Vec is an oncolytic immunotherapy with therapeutic potential, we believe, in several hard-to-treat cancers. In addition to moving the program into Phase 3 testing in liver cancer, for which today there is only one approved product, we will be exploring its potential in other cancer types and in combination with other therapies, such as immune checkpoint inhibitors.”
Dr. Benjamin Li, Chief Executive Officer of Lee’s Pharmaceutical, said: “China has the highest prevalence in liver cancer (HCC) in the world and despite recent advancement in targeted therapy, significant medical need remains unmet. Pexa-Vec’s oncolytic immunotherapy approach has been shown in a previous Phase 2 study as a promising first line treatment option for advanced liver cancer patients. We look forward to starting the Phase 3 clinical trial with our partners in 2015 to validate the potential of this exciting agent and work towards a better management of advanced HCC in China.”
To date, over 300 patients have been treated with Pexa-Vec. Additional data supporting the activity of Pexa-Vec across different tumor types is expected to be presented at upcoming medical conferences later this year.
Lead Program – The planned Phase 3 trial will assess Pexa-Vec followed by sorafenib in the first-line treatment of patients with advanced HCC. This global study will be conducted in Europe, Asia and North America. It is expected to enroll approximately 600 patients. Patients will be randomized 1:1 to either receive Pexa-Vec immediately followed by sorafenib or to receive sorafenib alone. Sorafenib (Nexavar®) is currently considered the global standard of care and is the only product approved for the first-line treatment of advanced HCC. The study is expected to start recruitment by mid-2015.
Additional Studies – In addition and as previously announced, a study evaluating Pexa-Vec and metronomic doses of cyclophosphamide in solid tumors, mainly in breast cancer and soft tissue sarcoma, is planned to be initiated this year. The study is being funded by the Institut National du Cancer (INCa) and sponsored by the Bergonié Institute (Bordeaux, France). Cyclophosphamide given at metronomic doses is used classically in combination with immunotherapeutics to potentiate their activity.
Other trials to complement and strengthen the program are also planned and include:
- A trial in the pre-surgery (neo-adjuvant) setting in solid tumors to gain a better understanding of Pexa-Vec activity in the actual tumor environment.
- A trial evaluating Pexa-Vec in combination with an immune checkpoint inhibitor, based on the rationale of gaining synergy and potency in combining two immunotherapy classes. This type of combination approach holds high promise in oncology.
The partners are also considering a Phase 1/2 study in combination with sunitinib malate (Sutent®) for renal cell cancer.
Commented Dr. Tae-Ho Hwang, SillaJen co-founder and Chief Scientific Officer: “We anticipate a number of these early exploratory studies will be performed in collaboration with Pusan National University Yangsan Hospital (PNUYH). The excellent team at PNUYH has been very supportive of the Pexa-Vec program and has demonstrated an ability to enroll patients quickly and conduct studies efficiently. We believe open collaboration and innovation by both the Company and Hospital is very important to lead promising immunotherapeutics such as Pexa-Vec to the clinic and we look forward to building on this progress as we move forward.”
Pexa-Vec (JX594/TG6006 pexastimogene devacirepvec) is an engineered oncolytic vaccinia virus armed with a GM-CSF gene that promotes an anti-tumor immune response. Pexa-Vec is designed to selectively target and destroy cancer cells through three different mechanisms of action: the lysis (breakdown) of cancer cells through viral replication, the reduction of the blood supply to tumors through vascular disruption, and the stimulation of the body’s immune response against cancer cells. Clinical trials are ongoing or planned in hepatocellular carcinoma (liver cancer), renal cell carcinoma (kidney cancer), as well as other tumor types.
Hepatocellular carcinoma, the lead indication for Pexa-Vec, is the fifth most common cancer worldwide and the third leading cause of cancer death, with over 600,000 new cases diagnosed annually resulting in more than 90 percent mortality.1 The annual incidence rate in the U.S., Europe, Japan and China are estimated to be 20,000, 55,000, 40,000 and 350,000 patients, respectively.2 Currently, there are few approved treatment options for advanced HCC patients.
Jennerex, Inc. has partnered with Transgene and Lee’s Pharmaceutical to develop and commercialize Pexa-Vec in major markets outside of the United States. Under existing agreements, Transgene has exclusive rights to develop and commercialize Pexa-Vec for the treatment of solid tumors in Europe, the Commonwealth of Independent States and the Middle East, while Lee’s Pharmaceutical retains exclusive development and commercial rights in Hong Kong and The People’s Republic of China.
See the press release here.