This phase II trial studies how well a cancer vaccine called STEMVAC works in combination with chemotherapy in treating patients with PD-L1 negative, triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that are expressed on breast cancer stem cells, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving STEMVAC in combination with chemotherapy may be an effective treatment for PD-L1 negative metastatic triple-negative breast cancer.
Patients must be at least ≥ 18 years of age
Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients < 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable
Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2
Histologically confirmed triple-negative breast cancer
Patient has received more than one line of prior therapy in metastatic setting
Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay
Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed. Participation in a trial for chimeric antigen receptor (CAR)-T cell therapy may be permitted if the CAR-T cell therapy is not planned to occur until after the currently proposed treatment (i.e. no longer participating in STEMVAC and chemotherapy trial)
Symptomatic restrictive cardiomyopathy
Single group
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Biological/VaccineGiven ID
Chemotherapy
DrugGiven standard of care chemotherapy
Computed Tomography
Procedure/SurgeryUndergo CT scans
Sargramostim
Biological/VaccineGiven ID
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Positron Emission Tomography (PET)
Procedure/SurgeryUndergo PET scan
Image Guided Biopsy
Procedure/SurgeryUndergo image-guided biopsy
Incidence of immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC): Incidence of patients who develop a positive immunogenic response after vaccination
The Th1 STEMVAC antigen specific immune response will be determined by IFN-gamma ELISPOT. Magnitude of Th1 response will be defined for each antigen in STEMVAC for each patient as the value of the corrected spots per well (CSPW) (CSPW= \[(mean of spots in the antigen stimulated wells) - (mean of antigens for the no-antigen negative control wells)\] for the same time point). Patients are considered to have preexisting immune response if the mean of spots in antigen wells is greater than the mean + 2 standard deviations of no-antigen wells at baseline. Patients are considered to have generated or enhanced antigen specific immunity post-vaccine if the maximal corrected IFN-gamma response post-vaccine is greater than the mean + 2 standard deviations of the baseline level (p \< 0.05). A patient will be considered an immunogenic responder if they develop an antigen-specific immune response to at least 1 of the 5 vaccine antigens.
Incidence of adverse events
Will be determined by chemical and clinical parameters evaluated at various time points. Toxicity grading will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 6.0 and monitoring of adverse events will be done per Food and Drug Administration and NCI guidelines. Descriptive statistics will be provided on the key demographic and clinical variables, such as mean, standard deviation, and range for continuous variables, and percent and number for categorical variables, such as toxicity grades.
6-month overall response rate
Will evaluate the clinical response to treatment following the first booster dose of STEMVAC using standard of care imaging and RECIST 1.1.
Progression-free survival (PFS)
Will evaluate the real-world progression-free survival to first subsequent therapy, defined as the date of first subsequent therapy after STEMVAC immunization and chemotherapy to disease progression, initiation of hospice or death as extracted from clinical notes.
Overall survival (OS)
Overall survival will be defined by patient survival or death from the start of treatment.
Magnitude of immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC)
Defined as the sum of the interferon gamma enzyme-linked immunosorbent spot of all STEMVAC antigens on blood samples collected pre-vaccine as compared to 1-month post dose #3 of the STEMVAC vaccine and again after 2 booster doses of STEMVAC vaccine. The magnitude of immunity will be calculated as the sum of antigen-specific immune responses across the five vaccine antigens. The mean and maximum post-vaccine immune responses will be summarized and compared with pre-treatment levels. If substantial outliers are present or the data are non-normally distributed, the Wilcoxon signed-rank test will be used to assess differences between pre-treatment and post-vaccine priming samples.
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University of Washington
Lead sponsor
Kuni Foundation
Collaborator
