March 23, 2021:

Rutgers Cancer Institute of New Jersey is leading a single-arm, phase II study for adults with advanced hepatocellular carcinoma and mild liver impairment.

Researchers want to learn whether it is safe to give atezolizumab and bevacizumab to participants with advanced liver cancer and Child-Pugh B7 liver dysfunction. They also plan to estimate the overall response rate, disease control rate, duration of response, progression-free survival, and overall survival in these patients using this combined therapy.

The study, BTCRC-GI20-457, “A Phase II study of Atezolizumab and Bevacizumab in Child-Pugh B7 Hepatocellular Carcinoma (The AB7 Trial),” is now open to accrual at Rutgers Cancer Institute of New Jersey.

In a prior study, the phase III IMbrave150 trial, atezolizumab plus bevacizumab was shown to improve response rates over standard therapy in patients with advanced or metastatic hepatocellular carcinoma (HCC). However, subjects with Child-Pugh B classification, which make up about 20-30 percent of patients with previously untreated disease, were excluded from this and other studies. The AB7 study will address an unmet need for this patient population.

While HCC is relatively rare in the United States, both the incidence and death rate of HCC have risen over the past decade. The majority of HCC cases in the United States are attributed to Hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease. Unfortunately, HCC is currently the fastest-increasing cancer-related cause death in the United States, with only 18 percent of patients surviving five years after their diagnosis.

Prior to the FDA approval of sorafenib, a tyrosine kinase inhibitor (TKI), in 2007, there was no standard treatment for patients with unresectable advanced or metastatic HCC. Several additional systemic therapies have since been approved. However median overall survival remains 1 year or less with TKI therapies.

Investigators say that there is evidence that combining atezolizumab and bevacizumab can shrink or stabilize untreated liver cancer, but they do not know whether the study drugs are safe to give to subjects with liver dysfunction.

“The goal of this study is to provide much needed safety information about this combination in these particular patients,” said Kristen Spencer, DO, MPH (pictured left), sponsor-investigator of the study and a medical oncologist in the Liver Cancer and Bile Duct Program at Rutgers Cancer Institute of New Jersey.

The study will also explore circulating tumor DNA (ctDNA) as a way to help measure how the tumor is responding to treatment. “Cancers are always shedding fragments of their DNA into the bloodstream,” Dr. Spencer said. “Being able to detect ctDNA helps us give a better representation of the changes that are happening in the tumor DNA more broadly than, for instance, a biopsy might. This approach is also less invasive and could become an earlier measure than what we typically use, such as tumor markers or radiographic imaging.”

Dr. Spencer said this study is going to be largely modeled after the IMbrave study. The primary objective will look at grades 3 to 5 treatment-related adverse events.

“The expectation is that while these events might be somewhat more frequent in this population, it will still be considered acceptable and safe to use in these patients,” said Dr. Spencer, who is also an assistant professor of medicine at Rutgers Robert Wood Johnson Medical School.

Her mentor, Howard S. Hochster, MD, FACP (pictured right), Associate Director for Clinical Research and director of the Gastrointestinal Oncology Program at Rutgers Cancer Institute, provided critical input in the design and conduct of the AB7 Trial.

“In this study, there is no placebo or randomization,” noted Dr. Hochster, who is also Director for clinical oncology research at RWJBarnabas Health and Distinguished Professor of Medicine at Rutgers Robert Wood Johnson Medical School. “We do not need randomization, as the original IMbrave150 study compared the immunotherapy drug atezolizumab with an anti-blood vessel drug, bevacizumab, to a standard treatment, sorafenib. It reduced the chance for death for the whole study by 42 percent, improving survival. In this study we are using the same combination in patients with mild liver dysfunction who were excluded in the original study to ensure the combination will be safe for these patients.”

Atezolizumab is a PD-L1 inhibitor that helps the immune system recognize and kill cancer cells. Bevacizumab is an anti-angiogenic therapy that can help prevent the formation of blood vessels that feed cancerous tumors. The combination is intended to prime the immune system and augment a response, Dr. Spencer said.

Atezolizumab and bevacizumab in combination is approved by the U.S. Food & Drug Administration for patients with unresectable or metastatic HCC who have not received prior systemic therapy. However, this combination has not been approved for patients with unresectable advanced or metastatic HCC with liver dysfunction and should be considered investigational.

All study participants will receive atezolizumab and bevacizumab intravenously once every three weeks. Treatment will continue until the cancer starts to grow or the patient experiences severe side effects. Participants may continue the treatment until their cancer gets worse or they have severe side effects. Subjects may withdraw from the study at any time in cooperation with their treating physician.

The AB7 Trial is supported by Genentech. The study will enroll up to 50 subjects.

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

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