our global Phase 3 trial is currently enrolling people with advanced liver cancer (hepatocellular carcinoma or HCC) who have never received systemic medicine (affecting the entire body) for advanced liver cancer. The PHOCUS study will measure survival in patients who receive Pexa-Vec followed by Nexavar® (sorafenib) compared to patients who receive Nexavar® alone. Patients with advanced hepatocellular carcinoma (HCC) currently have few systemic therapies that are effective in treating the disease.
In the US, while death rates from most major cancers are declining, the incidence and associated death from liver cancer is on the rise. The American Cancer Society estimates that in the year 2016, approximately 39,000 people in the US will be diagnosed with liver cancer and approximately 27,000 will die from liver cancer.1
Liver cancer is a cancer that originates in the cells in the liver. Hepatocellular carcinoma (HCC), the most common liver cancer, originates in hepatocytes; other less common types of liver cancer are intrahepatic cholangiocarcinoma and hepatoblastoma. Cancer that started in a different organ of the body such as the lung or breast and then spread to the liver is called metastatic cancer, and is not considered liver cancer.
In all regions of the world the incidence of liver cancer in men is two to three-fold higher than in in women.2 In general, cirrhosis of the liver is associated with an increased risk of developing liver cancer. Cirrhosis can be caused by many factors including chronic infection with Hepatitis B virus or Hepatitis C virus (HCV), excessive alcohol use, non-alcoholic fatty liver disease, obesity, type 2 diabetes, certain autoimmune diseases, and certain rare genetic disorders (e.g. hemochromatosis).2 In the US, metabolic disorders are now the greatest risk factors for HCC accounting for up to 32% of cases, while up to 20% of HCC cases are associated with HCV infection. Identifying and treating those at highest risk for cirrhosis may help to reduce the incidence and mortality of liver cancer.
When liver cancer is diagnosed early, surgery or liver transplantation are effective treatment options, with a 5-year overall survival rate of ≥ 50%.3 For patients who are not candidates for liver transplantation or surgical resection, a number of loco-regional therapies are available including percutaneous ethanol injection therapy (PEIT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and radio-embolization. 4
For late stage patients the treatment options are limited; Sorafenib, (Nexavar®) is the only approved systemic treatment for late stage patients. Sorafenib is an oral pill that inhibits multiple kinases including RAF/MEK/ERK pathway kinases and VEGFR/PDGFR tyrosine kinases. Inhibiting these pathways slows cell proliferation and the growth of new blood vessels. In a phase 3 clinical trial, treatment with sorafenib prolonged survival and time to progression by 3 months. 5
New immunotherapy treatments are actively being investigated in clinical trials. These investigational treatments include: immune checkpoint inhibitors, monoclonal antibodies, adoptive T-cell therapy and oncolytic viruses. Oncolytic viruses such the investigational product Pexa-Vec, are viruses that were engineered to preferentially infect and replicate within tumor cells. The viruses can be engineered so that they also express therapeutic transgenes; 6 Pexa-Vec was engineered to produce GM-CSF, which may induce a systemic anti-tumor immune response. Pexa-Vec, with its unique mechanism of action, has the potential to be synergistic with approved cancer drugs and new drugs currently in development, in particular with immunotherapies that can be administered in combination. Pexa-Vec is currently being evaluated in our global Phase 3 trial.
2 McGlynn KA and London WT, Clin Liver Dis 2011
3 Bruix J et al., Oncogene 2006
4 Bruix J and Sherman M, AASLD Guideline 2011
5 Llovet JM et al., N Engl J Med 2008
6 Bauzon M and Hermiston T, Front Immunol 2014