This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic acid (DNA) plasmid-based vaccine in treating patients with human epidermal growth factor receptor 2 (HER2)-negative stage III-IV breast cancer. Multiantigen DNA plasmid-based vaccine may target immunogenic proteins expressed in breast cancer stem cells which are the component of breast cancer that is resistant to chemotherapy and has the ability to spread. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 4 arms. Arm 1: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) as 1 injection intradermally (ID) every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression. ARM 2: Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression. ARM 3: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression. ARM 4: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression. After completion of study treatment, patients are followed up twice yearly for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Given ID
Correlative studies
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Incidence of toxicity per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 4.0
The type and grade of toxicities noted during the immunization regimen will be summarized. Adverse events noted by the investigator/designated clinical research staff will be tabulated according to the affected body system. Descriptive statistics will be used to summarize changes from baseline in clinical and/or laboratory parameters.
Time frame: Up to 1 month after last vaccine
Immunologic efficacy defined as achievement of a statistically significant increase in Th1 cell immunity for at least 50% of the immunizing antigens as compared to baseline
Time frame: Up to 5 years
Memory Th1 dominant immune response to all five antigens over time
Time frame: Up to 12 months
Modulation of T-regulatory (Treg) cells with vaccination
Treg defined as present or absent, and the probability will be estimated as a simple proportion.
Time frame: Up to 12 months
Modulation of MDSC with vaccination
MDSC defined as present or absent, and the probability will be estimated as a simple proportion.
Time frame: Up to 12 months
STEMVAC specific Type 1 immune response
Will detect if STEMVAC specific Type 1 immune response would be negatively correlated with the type II bacterial-tumor antigen (Bac-TA) specific responses. Statistical strategies will be used to assess the incidence and breadth of vaccine induced immunity as related to the levels of Bac-TA Th2 (Arm 4). For magnitude, the initial analysis could include two-tailed Pearson's correlation or even two tailed T tests between clear responder and non-responders. Specific organisms in the gut microbiome may prevent the development of tumor specific Type I immunity after vaccination, and will be evaluated by flow cytometry of peripheral blood mononuclear cells. Analysis could identify a blood based biomarker (Bac-TA responses) that could identify patients who would be less responsive to immune modulation and will be assessed by shotgun metagenomic sequencing.
Time frame: Up to 12 months
Bac-TA cross-reactive T-cells
Will evaluate whether organisms associated with Bac-TA cross-reactive T-cells are represented in the patient's microbiome. Will be assessed by collecting stool with the OMNIgene-GUT collection Kits (DNA Genotek) (Arm 4). Analysis could identify a blood based biomarker (Bac-TA responses) that could identify patients who would be less responsive to immune modulation and will be assessed by shotgun metagenomic sequencing.
Time frame: Up to 12 months
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