Experimental Antibody for Treatment-Resistant Liver Cancer
Name of the Trial
Phase II Study of TRC105 in Patients with Hepatocellular Carcinoma (HCC) Who Have Progressed on Sorafenib (NCI-11-C-0181). See the protocol summary.
Dr. Tim Greten, NCI Center for Cancer Research
Why This Trial Is Important
Liver cancer is the sixth most common type of cancer and the third leading cause of cancer death worldwide. Although it is relatively rare in the United States, its incidence has been increasing steadily. Among the various types of liver cancer, hepatocellular carcinoma and cholangiocarcinoma are the two main types diagnosed in adults, with hepatocellular carcinoma accounting for roughly three-quarters of cases.
Surgery (resection) to remove the tumor is the preferred treatment for patients with early-stage hepatocellular carcinoma. Unfortunately, most patients are ineligible for surgery because of the location of the tumor within the liver and/or coexisting medical conditions, such as cirrhosis.
Patients with unresectable, localized hepatocellular carcinoma may be treated with other types of local therapy, such as radiofrequency ablation, transarterial chemoembolization, or liver transplantation. In some cases, these treatments may lead to longer survival. Until recently, however, systemic therapies have offered little benefit for patients with unresectable liver cancer.
A phase III trial in 2008 showed that patients with advanced disease who received the drug sorafenib—a multikinase inhibitor that blocks important molecular pathways in the tumor cell and inhibits tumor angiogenesis (the growth of new blood vessels to a tumor)—tended to live longer and experienced a longer time to progression than those who received a placebo. Not all patients benefit from sorafenib therapy, though, and doctors are eager to find more effective systemic agents for liver cancer.
TRC105 is an experimental monoclonal antibody with a strong rationale for use in hepatocellular cancer. Like sorafenib, TRC105 interferes with a tumor’s ability to recruit the new blood vessels necessary for growth, but TRC105 targets a different molecular pathway than those targeted by sorafenib.
In this trial, patients with unresectable hepatocellular carcinoma who are ineligible for liver transplants or other localized therapies, and who did not benefit from or could not tolerate treatment with sorafenib, will be treated with intravenous TRC105 every 2 weeks. Doctors will assess the patients’ stage of disease every 8 weeks and determine the time to disease progression.
“Hepatocellular carcinomas are highly vascularized tumors of the liver, and we know from our experience with sorafenib that targeting angiogenesis is a potentially effective strategy,” said Dr. Greten.
“TRC105 is an antibody that recognizes and binds to a molecule called endoglin, or CD105, that is expressed on proliferating endothelial cells within the tumor. Endoglin is a receptor protein that plays a critical role in tumor angiogenesis. Once TRC105 binds to endoglin, it activates the immune system to destroy the endothelial cells,” he explained.