Dr Brufsky on the Unique Design of the Allogeneic SV-BR-1-GM Vaccine in Metastatic Breast Cancer

Adam M. Brufsky, MD, PhD, FACP, professor, medicine, associate division chief, Division of Hematology/Oncology, Department of Medicine, the University of Pittsburgh School of Medicine; medical director, the Magee-Women's Cancer Program, associate director, clinical investigations, codirector, the Comprehensive Breast Cancer Center, UPMC Hillman Cancer Center, discusses the unique design of the allogeneic GM-CSF–secreting breast cancer vaccine SV-BR-1-GM, highlighting how this agent distinguishes itself from other currently available agents in the metastatic setting.

SV-BR-1-GM is a genetically engineered human breast cancer cell line clinically used as a targeted immunotherapy in advanced metastatic breast cancer, Brufsky begins. The vaccine consists of irradiated allogeneic breast cancer cells derived from the SV-BR-1 cell line and transfected with the granulocyte-macrophage colony-stimulating factor (GM-CSF; CSF2) gene. Unlike CAR T-cell therapy, which involves modifying and reinfusing a patient’s own cells, SV-BR-1-GM is an off-the-shelf allogeneic product, he notes.

SV-BR-1-GM is being evaluated as part of the Bria-IMT regimen in the phase 3 BRIA-ABC trial (NCT06072612). The Bria-IMT regimen includes administering 300 mg/m2 of cyclophosphamide on day -2 or -3 along with 4 intradermal inoculations of SV-BR-1-GM on day 0. The mechanism of action is under investigation, although it is hypothesized that, upon intradermal administration, the genetically modified SV-BR-1-GM cells secrete GM-CSF, potentiating a tumor-specific cytotoxic T-lymphocyte immune response against breast cancer cells. Approximately 90% of patients have a partial HLA match with the product, which allows the vaccine to activate an immune response against their breast cancer cells, Brufsky adds.

Early data reported from the study showed early activity with the regimen, which produced a 71% intracranial objective response rate in patients with heavily pretreated advanced breast cancer and central nervous system (CNS) metastases. Based on these findings, a pre-planned subgroup analysis of patients with CNS metastases in advanced metastatic breast cancer is planned for the phase 3 trial. This analysis could provide additional indications for market approval of Bria-IMT, potentially expanding its use in advanced metastatic breast cancer.