Neoantigen DNA Vaccine Alone vs. Neoantigen DNA Vaccine Plus Durvalumab in Triple Negative Breast Cancer Patients Following Standard of Care Therapy

Histologically confirmed diagnosis of invasive breast cancer.

ER and PR less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor. Patients not meeting this pathology criteria, but have been clinically treated as having TNBC, may be enrolled at treating physician's discretion.

HER2 negative by FISH or IHC staining 0 or 1+.

Consented for genome sequencing

Clinical stage T1c-T4c, any N, M0 primary tumor by AJCC 7th edition clinical staging prior to neoadjuvant chemotherapy, with residual invasive breast cancer after neoadjuvant therapy.

At least 18 years of age.

Eastern Cooperative Oncology Group (ECOG) performance status ≥1.

Adequate organ and marrow function no more than 14 days prior to registration as defined below:

* absolute neutrophil count ≥1,500/μL

* platelets ≥100,000/μL

* hemoglobin ≥ 9.0 g/dL

* total bilirubin ≤ 1.5 X institutional upper limit of normal

* AST/ALT ≤2.5 X institutional upper limit of normal

* serum creatinine clearance \>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance

Body weight \> 30 kg.

Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

* Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

* Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

Able to understand and willing to sign an IRB-approved written informed consent document.

Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, evidence of any acute or chronic viral illness or disease, or psychiatric illness/social situation that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.

Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:

* Subjects with vitiligo or alopecia

* Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

* Any chronic skin condition that does not require systemic therapy

* Subjects without active disease in the last 5 years may be included but only after consultation with the study physician

* Subjects with celiac disease controlled by diet alone

History of pneumonitis or interstitial lung disease.

History of active primary immunodeficiency.

Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

History of allogeneic organ transplantation.

Pregnant or breastfeeding. A negative serum pregnancy test is required no more than 7 days before study entry.

Subjects of reproductive potential who are not willing to employ effective birth control from screening to 1 year after the last dose of durvalumab.

History of another primary malignancy except for:

* Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study treatment and low potential for risk of recurrence

* Adequately treated non-melanoma skin cancer of lentigo maligna without evidence of disease

* Adequately treated carcinoma in situ without evidence of disease

History of leptomeningeal carcinomatosis.

Patient must have no active major medical or psychosocial problems that could be complicated by study participation.

Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered.

Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.

Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.

Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.

Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, EKG, and/or laboratory screening test

Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child, or chronic seizure disorder which is well controlled by medication with no seizures within the last 2 years

Syncopal episode within 12 months of screening

Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.

What this study is about