This phase II trial studies the immunologic response and side effects of using the WOKVAC vaccine in combination with chemotherapy and HER2-targeted monoclonal antibody therapy before surgery in treating patients with breast cancer. Vaccines like WOKVAC are made from tumor-associated antigens which may help the body build an effective immune response to kill tumor cells. Chemotherapy drugs, such as paclitaxel, 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. Trastuzumab and pertuzumab are forms of targeted therapy because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab and pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving the WOKVAC vaccine at the same time (concurrently) with paclitaxel, trastuzumab, and pertuzumab before surgery may kill more tumor cells.
Patients must be at least >= 18 years of age
Clinical stage I-III breast cancer, HER2+ (per American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guideline update, 2018), regardless of estrogen receptor (ER)/ progesterone receptor (PR) status and planning to undergo neoadjuvant therapy with either paclitaxel, trastuzumab, and pertuzumab (THP) or docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)
Patients who have received prior neoadjuvant chemotherapy are allowed but may only receive paclitaxel, trastuzumab, and pertuzumab for the duration the study
Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
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
Single group
pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine
Biological/VaccineGiven ID
Paclitaxel
DrugGiven via infusion
Trastuzumab
Biological/VaccineGiven IV
Pertuzumab
Biological/VaccineGiven IV
Docetaxel
DrugGiven IV
Carboplatin
DrugGiven IV
Ultrasound Imaging
Procedure/SurgeryUndergo ultrasound imaging
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Enumeration of the number of T-bet+, CD4+, and CD8+ T-cells in tumor infiltrating lymphocytes (TIL) after combination immune-chemotherapy
Tumor tissue will be collected from prior diagnostic tumor biopsies as well as from an ultrasound guided core needle biopsy performed on day 13 of cycle 3. Tumor biopsies collected pre- and post- trial therapy will be processed and evaluated by immunohistochemistry for differences and changes in T cell content and T cell subtype. Specifically, will evaluate the differences in the presence of T-bet+ CD4+ and CD8+ T cells, a T cell subtype recently recognized to influence both the induced human epidermal growth factor receptor 2 (HER2)-specific cellular immunity and clinical outcomes. Changes in the tumor content of T-bet+ CD4+ and CD8+ T cells between the pre- and post-trial therapy time points will be evaluated.
Incidence of adverse events
Safety will be assessed per Common Terminology Criteria for Adverse Events version (v)4.0. 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 adverse events 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.
Induction of type 1 helper cell (Th1) immunity against HER2, IGF-1R, and IGFBP2
Cellular immune response will be defined by the magnitude of the Th1 (interferon-gamma \[IFN-g\]) versus (vs.) type 2 helper cell (Th2) (IL-10) antigen specific immune response using enzyme-linked immunosorbent spot assay (ELISPOT). Immune responses as measured by IFN-g ELISPOT will be summarized with mean and standard deviation or median and range 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. The proportion of study participants who develop immunity to either of the three antigens will be computed and 95% confidence internal would be generated. The induction of Th1 immunity will be compared against the presence or absence of a complete pathologic response to determine if there is a significant correlation using Pearson r correlation analysis.
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University of Washington
Lead sponsor
United States Department of Defense
Collaborator
