Hepatocellular carcinoma is an aggressive cancer that is often difficult to treat due to the typical accompanying diagnosis of cirrhosis. For patients who qualify for curative treatment, surgery and liver transplant may be considered. However, most patients are not eligible for curative therapy, and instead may be offered liver-directed or systemic therapies that may extend overall survival, but outcomes remain poor for these patients.

A new Hoosier Cancer Research Network study led by researchers at the University of North Carolina Lineberger Comprehensive Cancer Center will help determine whether adding an immunotherapy drug to standard local radiation therapy for patients with high-risk hepatocellular carcinoma could lead to further improvements in overall survival.

The open label, multi-center pilot study, known as HCRN GI15-225, will evaluate the safety and efficacy of giving the immune checkpoint inhibitor drug pembrolizumab in combination with Y90 radioembolization in patients with a poor prognosis who are not candidates for liver transplant or surgery.

The study is now open to accrual at the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C. Additional sites will open the study in the near future. Autumn McRee, MD, is leading the study, along with co-investigators Bert H. O’Neil, MD, and Matthew Johnson, MD, of Indiana University School of Medicine.

How the Drugs Work

The immune system includes certain cells called T cells that help the body to fight infections and other foreign cells. Unfortunately, cancer cells often express a protein called PD-L1 (programmed death-ligand 1), which binds to the PD-1 receptor on T cells, halting the killing function of these T cells.

Pembrolizumab is a type of immunotherapy that works by removing the brakes on the immune system, which then allows the immune system to fight the cancer.

Y90, also known as TheraSphere®, is one form of local radiation treatment that is delivered though a catheter into the liver. Y90 is made up of millions of tiny glass beads that contain radiation. When Y90 is injected into the catheter, the beads flow directly into the liver cancer and help destroy the tumor.

Dr. McRee notes previous studies have shown that radiotherapy in liver cancer can result in the enhanced expression of cell-death proteins.

“One hypothesis is that radiation therapy, whether given through an external beam or, in this case, through beads or spheres coated with radiation, may increase the number of those proteins or signals that the immune system recognizes in order to fight the cancer more effectively,” Dr. McRee said. “Through some of the correlative science embedded in this trial, we’re hoping to get a sense for what it is about the tumor and the immune system that may make some patients more susceptible to this than others.”

About the Study

This study will enroll 30 subjects. All participants will receive standard treatment with Y90 radioembolization and the study drug pembrolizumab. Pembrolizumab is approved by the U.S. Food and Drug Administration to treat other cancers, but it is not approved to treat hepatocellular carcinoma.

To enroll in HCRN GI15-225, subjects must have locally advanced hepatocellular carcinoma with a poor prognosis, have no evidence of extrahepatic metastatic disease, and have not received prior systemic anti-cancer therapies for their cancer. Additional eligibility requirements must be met to enroll.

For more information about this study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03099564).

This trial is supported by Merck Sharp & Dohme Corp.

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has initiated more than 160 trials in a variety of cancer types and supportive care, resulting in more than 300 publications. More than 5,000 subjects have participated in Hoosier Cancer Research Network clinical trials.