Neoadjuvant Dupilumab, Pembrolizumab, Paclitaxel, and Carboplatin in Locally Advanced Triple Negative Breast Cancer

Inclusion Criteria:

* Patients with pathologically confirmed diagnosis of triple negative breast cancer, as defined by the most recent ASCO/CAP guidelines.
* Patients must have previously untreated, localized TNBC with either tumor size ≥ 2 centimeters (T2-4N0) or lymph node involvement with at least a 1cm tumor (T1c-T4N1-3).
* Patients must have previously untreated disease with no prior definitive breast surgery, radiation therapy, or systemic chemotherapy with therapeutic intent for this breast cancer.
* Patients must be eligible to receive chemotherapy agents in the study including paclitaxel and carboplatin.
* Patients must be willing and able to provide blood samples at the time points indicated in the study calendar.
* Patients must be willing and able to have core needle biopsies of tumor prior to initiation of treatment. Should patients undergo pre-treatment or on-treatment biopsy procedure and inadequate number of biopsies are obtained, they may proceed with initiation/continuation of treatment at the discretion of the investigator and treating physician.
* Age ≥ 18 years.
* ECOG performance status 0-1.
* Adequate organ and marrow function as defined below:

  * absolute neutrophil count ≥ 1,500/mcL
  * platelets ≥ 100,000/mcl
  * total bilirubin within normal institutional limits
  * AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
  * creatinine within normal institutional limits
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
* Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or any treatment with therapeutic intent for the breast cancer.
* Patients may not be receiving any other investigational agents.
* Patients who have any distant metastases and considered to have Stage IV disease.
* Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
* Patients with active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.
* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, dupilumab or pembrolizumab used in study. Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps).
* HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<350 CD4+ T cells/microliter in the peripheral blood.
* Known active Hepatitis B (e.g., HBV detected by PCR or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
* Known, untreated helminth infections. Patients with prior history of a helminth infection who were fully treated are permitted.
* History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
* Receipt of a live vaccine within 30 days of planned start of study medication.
* History of irAE in response to prior immunotherapy that has not improved to a Grade 0 or 1; this does not include chronic conditions such as endocrinopathies which can be treated with hormone replacement therapy.
* History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. History of radiation pneumonitis treated with glucocorticoids.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.