This phase II trial evaluates whether a multi-antigen vaccine called STEMVAC improves disease-free survival after surgery in patients with triple-negative breast cancer (TNBC) and moderate or extensive residual cancer burden. TNBC has an aggressive clinical course and poorer disease-free survival compared to other subtypes. While patients who have no remaining tumor in the breast or lymph nodes after surgery have excellent long-term outcomes, patients with moderate or extensive residual cancer burden remain at high risk for early disease return and poorer prognosis. STEMVAC is designed to target proteins that tumor cells use when they become more aggressive and start to spread, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Giving STEMVAC after surgery may improve disease-free survival rates in TNBC patients with moderate or extensive residual cancer burden.
At least 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2
Triple-negative breast cancer as determined by the treating oncologist
Completed standard of care neoadjuvant chemotherapy in the opinion of their treating oncologist
Toxicities related to prior exposure to immune checkpoint inhibitors for which immune checkpoint inhibitors cannot be safely continued as determined by study investigator
Germline BRCA1 or BRCA2 mutations with adjuvant olaparib planned within the study period
NOTE: If olaparib is not planned, then these patients are eligible
Symptomatic restrictive cardiomyopathy
Parallel
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Biological/VaccineGiven ID
Recombinant Granulocyte-Macrophage Colony-Stimulating Factor
DrugGiven ID
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Invasive breast cancer free survival (IBCFS)
Kaplan-Meier curves will be generated with median estimation and 95% confidence interval, and log-rank tests will be conducted to compare the survival difference between groups. Will calculate the 3-year IBCFS rate with a 95% confidence interval from Kaplan-Meier methods using Greenwood standard errors.
Dynamics and characteristics of circulating tumor deoxyribonucleic acid (ctDNA)
Through serial ctDNA evaluation, each sample will be assessed for ctDNA detectability and, if detectable, total ctDNA mass (continuous variable, as reported by the assay platform) will be calculated. ctDNA detectability and quantitative ctDNA measures will be summarized descriptively by timepoint and study arm, and changes over time will be evaluated using methods appropriate to the final endpoint definition, data distribution, and repeated-measures structure of the data. Associations with IBCFS will also be explored. Copy number variants (including aneuploidy, chromosome-level gains, losses, and amplifications, as defined by the final assay methodology) will also be tracked and tabulated, and changes over time will be evaluated descriptively in both study arms.
Incidence of adverse events
Safety and systemic toxicity will be determined by clinical and laboratory parameters evaluated at protocol-specified time points. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0. The type and grade of toxicities observed during the immunization regimen will be summarized, and the duration of toxicities will be summarized using descriptive statistics. All adverse events reported by the investigator will be tabulated according to the affected body system. The frequency and severity of adverse events will be summarized using proportions and corresponding 95% confidence intervals. Demographic and baseline characteristics obtained at enrollment will be summarized in tabular and/or graphical formats using descriptive statistics.
Immune response
Immune response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine (STEMVAC) will be measured in peripheral blood functionally by IFN-g enzyme-linked immunosorbent spot, phenotypically using cytometry by time-of-flight to identify T-cell clonal populations, and genomically, using T-cell receptor beta sequencing of CD4+ CD8+ T-cells.
Expression of epithelial to mesenchymal transformation (EMT)-associated genes
EMT-associated gene expression profiles in residual triple negative breast cancer in surgical pathology samples will be defined for each patient with particular attention on STEMVAC antigen expression. Expression of these EMT-related genes will be assessed using RNA extracted from formalin-fixed paraffin-embedded tissue.
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University of Washington
Lead sponsor
United States Department of Defense
Collaborator
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