Anticancer agent - catumaxomab
Numerous antibody drugs have been developed to treat cancers, because they can be very specifically targeted at particular receptors and types of tumour.
Numerous antibody drugs have been developed to treat cancers, because they can be very specifically targeted at particular receptors and types of tumour.
Another that is being developed by Fresenius Biotech and Trion Pharma in Germany is catumaxomab, a trifunctional bispecific hybrid rat-mouse monoclonal antibody that targets both human Ep-CAM and human CD3.1 It activates both T cells and accessory immune cells and thus destroys tumour cells that have the surface antigen Ep-CAM, or epithelial cell adhesion molecule.
It has potential in several different types of cancer, including gastric and ovarian, as well as for the intraperitoneal treatment of malignant ascites, where fluid containing cancer cells collects in the abdomen.2 A Phase II/III trial was carried out in a total of 258 patients with Ep-CAM positive cancer and malignant ascites for whom chemotherapy could no longer be used. Half of the subjects had ovarian cancer, and a quarter gastrointestinal cancer. They were given intraperitoneal doses of the drug following paracentesis on days 0, 3, 7 and 10 in ascending doses of 10, 20, 50 and 150µg, or paracentesis on its own.
For the treatment group, the median time to the first therapeutic paracentesis or death was 46 days, compared with 11 days in the control group. The median time to disease progression was 111 days for those given the antibody, and 35 days for the control group. The best improvement was seen in those subjects with ovarian cancer.
The drug was safe and no deaths were attributed to the treatment regimen. There were mild to moderate changes in blood cell count and liver function, but few of these were clinically significant. The most common adverse event was abdominal pain, and side-effects related to cytokine release such as nausea, vomiting and fever.
It has also been investigated as a direct treatment for ovarian cancer. In a randomised trial, a total of 45 women with platinum refractory ovarian cancer were given four 10µg doses or four ascending doses of 10, 20, 50 and 100µg of the antibody intraperitoneally on days 0, 3, 7 and 10.3,4 Six patients in the high dose group showed a clinical response, compared to three in the lower dose group. Again, it was safe, with acceptable toxicity at the highest dose.
Several other trials are under way, including an open label Phase II study in ovarian cancer patients with recurring malignant ascites, and further trials as an adjuvant therapy after surgery in both ovarian and gastric cancer patients.