USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC, has launched a global registration, phase 2 clinical trial investigating the efficacy of a potential new breast cancer therapy called ARX788.

The trial is currently recruiting breast cancer patients whose cancer has metastasized (spread to other areas of the body) and whose tumors show increased levels of a protein called human epidermal growth factor receptor 2 (HER2). Participants must also have experienced resistance or disease progression while on treatment plans containing T-DM1, and/or T-DXd, and/or tucatinib, which are typically prescribed for HER2-positive breast cancer patients.

About 20% of breast cancers are HER2 positive. The HER2 protein promotes cancer cell growth, which can make HER2-positive breast cancer more aggressive and difficult to treat, despite the availability of therapeutic options specific to this type of cancer.

Chemotherapy may be used in combination with targeted therapies, but can cause difficult side effects because the drug is administered throughout the body rather than just to the areas affected by cancer.

“At USC Norris, we treat a large volume of patients with HER2-positive, metastatic breast cancer and we’ve found that resistance to existing therapies is a major issue,” said Janice Lu, MD, PhD, a medical oncologist with Keck Medicine, medical director of the USC comprehensive breast oncology program and global lead principal investigator of the trial. “We are excited to lead this effort in assessing a possible alternative solution for breast cancer patients, and hope to expand our ability to provide effective personalized care.”

Michael Press, MD, PhD, a pathologist with Keck Medicine, member of USC Norris and the director of the Breast Cancer Analysis Lab at the Keck School of Medicine of USC, will lead the study’s pathological evaluation.

ARX788 is an antibody drug conjugate, which is a type of therapy that combines a monoclonal antibody with a potent dose of medication, allowing for precise, targeted drug delivery that could potentially lessen side effects. ARX788 is designed with an anti-HER2 monoclonal antibody that identifies HER2-positive tumor cells to deliver a powerful dose of Amberstatin269, which destroys cancer cells and prevents new cells from forming.

Results from two phase 1 clinical trials demonstrated promising anti-tumor activity in patients who had previously received aggressive treatment plans, showing an overall response rate of 74% and a disease control rate of up to 100%, depending on dosing.  ARX788 was well-tolerated, with most adverse events being mild or moderate.

“If this drug is effective, it could provide a hopeful alternative to patients with a difficult prognosis and help them maintain a quality of life in ways that chemotherapy cannot,” said Lu, who is also a member of USC Norris.

The trial is currently recruiting participants at more than 20 sites across the United States and Australia, with plans to open 150 sites worldwide, including Europe and Asia.

Those interested in enrolling at the USC Norris site can contact (323) 865-BRST (323-865-2778). To learn more about USC Norris breast cancer research, treatment and prevention please visit the USC Breast Center.

The trial is sponsored by Ambrx, which manufactures ARX788. Those wishing to learn more about the trial can email [email protected].

This study will be presented at the San Antonio Breast Cancer Symposium on Dec. 7-10, 2021 as an ongoing trial.