A phase II study of the DNA plasmid-based vaccine STEMVAC in patients with metastatic triple-negative breast cancer (mTNBC).

TPS2698 Background: Adding immune checkpoint inhibitors for the treatment of mTNBC improves the efficacy of traditional chemotherapy in select populations. In populations who are not predicted to benefit from PD-1 checkpoint inhibitors, a vaccine may sensitize Th1 cells against cancer-associated antigens to facilitate immune-mediated tumor killing. STEMVAC is a safe, immunogenic plasmid DNA-based vaccine encoding T-helper 1 (Th1) selective epitopes from five antigens (MDM2, YB1, SOX2, CDH3, CD105) associated with breast cancer stem cells and the epithelial-mesenchymal transition. In addition to direct cytotoxic effects directed against cancer cells, we have demonstrated that vaccine-induced Th1 cells secrete IFN-γ, which upregulates suppressor of cytokine signaling 1 (SOCS1), leading to slowed tumor growth and increased vulnerability to cytotoxic agents. Combining STEMVAC with chemotherapy could thus have synergistic effects leading to enhanced cancer sensitivity to treatment and possible eradication. Methods: The study (NCT07078604) includes adults with PD-L1 negative mTNBC receiving standard therapies inclusive of chemotherapy, antibody-drug conjugates, and oral PARP inhibitors in the first and second line. Eligible patients will have histologically-confirmed mTNBC, radiographically measurable disease by RECIST v1.1, and a lesion amenable to biopsy. Key exclusion criteria include concomitant B-cell malignancies, ongoing systemic steroid use, and known hypersensitivity reaction to GM-CSF. Participants receive intradermal STEMVAC 300mcg with 100mcg of GM-CSF given during the nadir period of standard of care chemotherapy. Participants receive three priming vaccines given every 21-28 days concurrent with chemotherapy, followed by booster doses at 6 and 9 months then every six months thereafter. The primary endpoints are 1) observance of immunogenicity to one of the five vaccine antigens, measured by interferon-gamma enzyme-linked immunospot assay, and 2) safety. Secondary endpoints include objective response rate, real-world PFS2, overall survival, and magnitude of immunogenicity. Exploratory endpoints include quantitative levels of CD8+ infiltrating lymphocytes and expression of genes associated with epithelial-mesenchymal transition before and after vaccine priming. Current status: This trial is recruiting patients, with up to 20 patients expected to be recruited across multiple sites. Safety data and preliminary outcomes will be reported as they become available. This trial aims to evaluate whether STEMVAC would achieve clinically relevant immunogenicity when administered concurrently with chemotherapy for the treatment of mTNBC. The trial will evaluate the safety and preliminary efficacy of this novel combination and explore tumor-immune microenvironment biomarkers to gain mechanistic insight. Clinical trial information: NCT07078604 .