Grant to Fund CAR T-cell Trial for HER2-Positive BC with Brain Metastases

The California Institute for Regenerative Medicine (CIRM) has granted a $9.28 million award to a group of City of Hope researchers carrying out a first-in-human Phase 1 clinical trial testing the safety and efficacy of CAR T-cell therapy for the treatment of women with HER2-positive breast cancer that has spread to the brain.

“Our team’s goal is to develop a novel therapy for breast cancer patients with brain metastases who currently have no other effective treatments,” Saul Priceman, PhD, assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation and one of the lead investigators of the trial, said in a press release.

“This is a beautiful example of how early support from private donors and foundations helped to develop a therapy and initiate a trial we were desperate to bring to patients, and now this CIRM award funds the entire clinical trial and helps to leverage the knowledge gained here to further advance this therapy,” Priceman added.

Chimeric antigen receptor T-cell therapy, more commonly known as CAR T-cell therapy, is a type of immunotherapy in which a patient’s own T cells — immune cells with anti-cancer activity — are collected and engineered in the lab to recognize and eliminate cancer cells. The treated cells are then inserted back into the patient’s body to fight the tumor.

The pilot Phase 1 trial (NCT03696030), which opened for enrollment last year and is still recruiting patients, has been designed to evaluate the safety and effectiveness of CAR T-cell therapy for patients with breast cancer that has already spread to the brain and failed to be kept under control with other therapies.

“For a woman who already has breast cancer, learning that a brain tumor has developed can be a frightening diagnosis because there are few treatment options available. CAR T-cell therapy may be another tool in our fight against this devastating disease,” Jana Portnow, MD, City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research and lead clinical investigator of the trial, said in a 2018 news release about the trial’s launch.

During the trial, researchers will isolate T cells from participants’ blood samples and genetically modify them in a such a way that they will be able to recognize and destroy cancer cells producing large amounts of the HER2 protein on their surface.

“Our hope is that the HER2-specific CAR T-cell therapy will target and kill HER2-positive cancer cells, and safely and effectively treat brain metastases in these patients,” Priceman said.

The modified T cells will then be delivered back to patients through an injection into the brain’s ventricles, which are cavities in the center of the brain that are filled with fluid. This mode of administration was first used successfully at the City of Hope in patients with glioblastoma, one of the most aggressive types of brain tumors, receiving CAR T-cell therapy.

“Because this type of CAR T-cell delivery was found to be safe, City of Hope will now also use this route of administration for patients on this trial,” Priceman said.

CIRM had previously funded the preclinical research led by Priceman that set the stage for the authorization of the trial’s launch, which was granted by the U.S. Food and Drug Administration (FDA) in 2018.

City of Hope, a leader in the use of CAR T-cell therapies, licensed the patent holding rights of its HER2-specific CAR T-cell therapy to Mustang Bio, a company dedicated to the development of new immunotherapies based on proprietary CAR T-cell therapies and gene therapies for rare disorders, in 2017.