Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced that recruitment has been completed for the pivotal phase III EXPAND clinical trial investigating the efficacy of Erbitux (cetuximab) in treating patients with advanced gastric cancer. The international study has recruited more than 870 patients since commencing enrolment in 2008.
"Erbitux has shown promising efficacy in several phase II studies so there is strong rationale for larger scale investigation of the drug's efficacy in this disease," explained lead investigator Dr Florian Lordick, MD, Klinikum Braunschweig, Hannover Medical School, Germany. "Gastric cancer is known to be difficult to treat, therefore patients need new treatment options that exceed the benefit of classical chemotherapy."
EXPAND is a multi-centre, open label, randomized, controlled study taking place at 185 centres in 25 countries including Latin America, Europe, Asia-Pacific and Japan. The trial will assess the efficacy of Erbitux in combination with cisplatin and capecitabine chemotherapies as a 1st line treatment for patients with advanced/metastatic gastric adenocarcinoma, including gastroesophageal junction (GEJ) adenocarcinoma. The primary endpoint of the study is progression-free survival determined by an independent review.
Gastric cancer, also known as stomach cancer, is the second leading cause of cancer death in men and the fourth among women worldwide. Generally, gastric cancer rates are about twice as high in men as in women. Each year nearly 930,000 people worldwide are diagnosed with gastric cancer and approximately 700,000 die of the disease.
Gastric cancer is notoriously difficult to treat and is associated with a poor prognosis. In resectable gastric cancer, surgery is potentially curative, but the majority of patients present with late stage disease and are therefore candidates for palliative chemotherapy only.
Erbitux is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumour cells and the spread of tumours to new sites. It is also believed to inhibit the ability of tumour cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumours, which appears to lead to an overall suppression of tumour growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in 82 countries. It has been approved for the treatment of colorectal cancer in 82 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 79 countries:
Merck licensed the right to market Erbitux outside the US and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT (tegafur-uracil) - an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.
Merck is also investigating among other potential cancer treatments the use of Stimuvax (BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Seattle, Washington, USA.
In addition, Merck is developing cilengitide, which is the first in a new class of investigational anti-cancer therapies called integrin inhibitors to reach Phase III development; it is currently being investigated for the treatment of glioblastoma, SCCHN and NSCLC. Integrin inhibitors are thought to work by targeting the tumour and its vasculature.
Merck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. In the United States and Canada, EMD Serono operates through separately incorporated affiliates.