A Hoosier Cancer Research Network study is testing a treatment combination for patients with gastric or esophageal cancer. The phase II study, HCRN GI17-319, focuses on adult patients whose cancer cannot be removed by surgery or has metastasized, and possess an amplification of the gene known as human epidermal growth factor receptor 2 (HER2).

The study, “A single arm, multi-center Phase 2 trial of mFOLFOX6 + trastuzumab + avelumab in first-line, metastatic, HER2-amplified gastric and esophageal adenocarcinomas,” explores whether adding avelumab, a PD-L1-targeting drug to chemotherapy and trastuzumab, a HER2-targeted therapy, will control a patient’s cancer for a longer period compared to the current standard treatment. It will also test the safety and tolerability of this combined therapy.

Patients with gastric cancer and esophageal cancer who are resistant to therapy currently have few options. They are typically treated with the chemotherapy regimen, mFOLFOX6 and a HER2-directed therapy, such as trastuzumab, if an amplification of the gene is present.

“The goal of this trial is to improve on the effectiveness of this class of drugs and improve on the standard of care in the first line of therapy by combining them together,” said Michael S. Lee, MD, sponsor-investigator of the research study and an oncologist at the University of North Carolina Lineberger Comprehensive Cancer Center. “We know there is a limited duration of benefit with the current standard treatment, and so we are seeking to add the immunotherapy drug avelumab with the aim of improving outcomes.”

The study is open to accrual at University of North Carolina at Chapel Hill; Robert H. Lurie Comprehensive Cancer Center at Northwestern University; Roswell Park Cancer Institute; University of Iowa Holden Comprehensive Cancer Center; Winship Cancer Institute of Emory University; City of Hope in Duarte, Calif.; and Atlantic Health System in Morristown, N.J. To participate in the study, adult patients must be 18 and older, have gastric or esophageal cancer that has metastasized or is inoperable and have an amplification of the HER2 gene.

Participants will receive up to 9 cycles of initial treatment, with each cycle lasting 14 days. This treatment will consist of the chemotherapy regimen mFOLFOX6, trastuzumab, and avelumab. Participants who experience a sustained response to treatment or stable disease after 9 cycles may then continue maintenance therapy, consisting of trastuzumab and avelumab, until their disease progresses or they can no longer tolerate treatment. Participants may stop treatment at any time.

Trastuzumab is approved by the U.S. Food & Drug Administration (FDA) for the treatment of HER2-overexpressing breast, gastric, and gastroesophageal junction cancer. Avelumab is FDA-approved for treating metastatic Merkel cell carcinoma and previously treated locally advanced or metastatic urothelial carcinoma. The combination of avelumab, trastuzumab, and chemotherapy to treat gastric or esophageal cancer is investigational.

Correlative objectives for this study will help researchers understand which patients may respond better to treatment and gain a greater understanding of cell activity throughout treatment. Researchers will collect biopsy tissue of the tumor and blood and stool samples.

Support for this study is provided by EMD Serono.

Dr. Lee encourages patients with stage IV gastric or esophageal cancer to be tested for HER2 gene amplification.

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03783936).

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 conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.