This phase II trial studies how well a vaccine, STEMVAC, works in combination with standard endocrine-based therapy (ET) with a CDK4/6 targeted drug therapy, or with the chemotherapy drug capecitabine, in treating patients with hormone receptor (HR)-positive, HER2-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 cancer 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. Standard ET is treatment that adds, blocks, or removes hormones in order to slow or stop the growth of cancer. Standard CDK4/6 inhibitors, including abemaciclib, may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Giving STEMVAC in combination with standard ET or chemotherapy may be an effective treatment for metastatic HR positive, HER2 negative breast cancer.
Patients must be at least ≥ 18 years of age
Histologically confirmed hormone receptor positive metastatic breast cancer: Tumors that are positive for estrogen receptor (ER) and/or progesterone receptor (PR)
0-1+ HER2 expression by immunohistochemistry (IHC) OR
Fluorescence in situ hybridization (FISH) negative OR
Symptomatic restrictive cardiomyopathy
Dilated cardiomyopathy
Unstable angina within 4 months prior to enrollment
New York Heart Association functional class III-IV heart failure on active treatment
Parallel
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Biological/VaccineGiven ID
Capecitabine
DrugGiven SOC capecitabine
Computed Tomography
Procedure/SurgeryUndergo CT or ultrasound-guided biopsies
Cyclin-Dependent Kinase 4 Inhibitor
DrugGiven SOC CDK4/6i
Cyclin-Dependent Kinase 6 Inhibitor
DrugGiven SOC CDK4/6i
F-18 16 Alpha-Fluoroestradiol
DrugUndergo FES PET
Hormone Therapy
DrugGiven SOC ET
Positron Emission Tomography
Procedure/SurgeryUndergo PET or FES PET
Biopsy Procedure
Procedure/SurgeryUndergo image-guided biopsies
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Abemaciclib
DrugGiven SOC abemaciclib
Incidence of adverse events (AEs)
Safety and systemic toxicity 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 AEs will be done per Food and Drug Administration and NCI guidelines. The type and grade of toxicities noted during the immunization regimen will be summarized. The duration of toxicities will also be summarized using descriptive statistics such as mean and standard deviation. All AEs noted by the investigator will be tabulated according to the affected body system. The frequency and severity of adverse events will be summarized with a proportion and a 95% confidence interval (CI).
Incidence of immunogenicity
Will be 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. Both incidence and magnitude will be assessed. Immune responses will be summarized with mean and standard deviation or median and range (if skewness is observed) over time, the change over time will be summarized with graphs, and also analyzed using linear mixed-effects regression models with normalizing transformation if necessary.
Progression-free survival (PFS)
Will be analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) will be computed.
Circulating tumor DNA (ctDNA)
Will evaluate persistence and level of ctDNA over time in peripheral blood with addition of STEMVAC at baseline, after completion of priming monthly doses, at booster vaccines, and at progression (end of study). Linear mixed-effects regression models with normalizing transformation (if necessary) will be employed to evaluate changes in ctDNA levels over time. Paired t test or Wilcoxon signed rank tests will be applied for pairwise comparisons (depending on the distribution) between time points.
Elimination of cancer cells associated with epithelial to mesenchymal transformation (EMT)
Will determine whether STEMVAC immunization in addition to either endocrine therapy plus a CDK4/6 inhibitor or capecitabine results in elimination of cancer cells associated with EMT, as EMT proteins are targeted by this vaccine. Will determine EMT signature by gene expression profiling in baseline tumor (previously collected tumor biopsy) and compare with post-STEMVAC tumor biopsy. Gene expression profiles from biopsies before and after vaccination will be compared using paired t test or Wilcoxon signed-rank test (depending on the distribution) to determine if vaccination modulates the EMT gene signature in the tumor. Differential gene expression analysis or linear models will be used to analyze individual EMT gene expression levels.
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