Clinical trial shows safety and effectiveness of new combination immunotherapy for advanced liver cancer


These CT scans of a 61-year-old man with hepatocellular carcinoma show tumor shrinkage after treatment with a combination immunotherapy. Photo courtesy of Tim Greten, M.D.

A recently completed phase I clinical trial at the NIH Clinical Center in Bethesda, Maryland, demonstrates that a combination of two immunotherapy drugs to target hepatocellular carcinoma (HCC) was well-tolerated and shrunk tumors in a larger percentage of patients than the standard monotherapy. Read more about other CCR clinical trials studying combination HCC therapies.

HCC is the most common form of liver cancer and the third-leading cause of cancer deaths worldwide, but few effective treatments exist for the advanced form of the disease. Currently, a drug called sorafenib is one of only two drugs approved to treat advanced HCC.

In the study, published online May 2, 2017, in Clinical Cancer Research, researchers gave 25 patients a combination of sorafenib plus a monoclonal antibody named TRC105. Both drugs are thought to disrupt blood vessel growth in HCC tumors, which are particularly susceptible to disruptions because they have a much faster rate of blood vessel growth than normal tissues. The drug combination effectively shrunk tumors in 25 percent of patients. In contrast, previous studies had shown that sorafenib by itself caused tumor shrinkage in only 3 percent of patients while TRC105 used by itself caused no improvement.

It is unclear why the combination treatment works better than either drug alone, but Tim Greten, M.D., Senior Investigator in the Thoracic and Gastrointestinal Oncology Branch, and a lead investigator on the study, suspects that sorafenib causes an increase in the expression of the receptor endoglin on HCC cells. TRC105 antibodies, which preferentially target endoglin receptors, then attack HCC cells with a greater ferocity that causes tumors to shrink.

Recruitment for a phase II clinical trial that seeks to confirm the results of the phase I study within the next year is underway. For more information on the new clinical trial, visit the clinical trials page.

Summary Posted: 05/2017