The AVIATOR Study: Trastuzumab and Vinorelbine With Avelumab OR Avelumab & Utomilumab in Advanced HER2+ Breast Cancer

Inclusion Criteria: * Age ≥18 years or older * Histologically confirmed breast adenocarcinoma that is unresectable loco-regionally advanced or metastatic * HER2-positive (immunohistochemistry score 3+) or ERBB2- amplification (Ratio ERBB2/centromeres ≥ 2.0 or mean gene copy number ≥ 6) on primary tumor or of metastatic or unresectable loco-regional biopsy. * Measurable disease per RECIST v1.1 (see Section 11) * Patients must have previous treatment with ado-trastuzumab emtansine (Kadcyla, T-DM1) in any setting. Patients must have previously received trastuzumab and pertuzumab in the metastatic setting or within 12 months of neoadjuvant/adjuvant treatment. * Patient must have progressed on their most recent line of therapy. Progression must have been demonstrated by radiological or clinical assessment. * Left ventricular ejection fraction (LVEF) ≥ 50% * Willingness and availability to submit FFPE tissue for central confirmation of HER2 positivity and central assessment of PD-L1 status. This can be from archival tissue from unresectable loco-regional or metastatic disease obtained ≤ 1 year prior to enrollment or new tissue material from a recently obtained surgical or diagnostic biopsy. Tissue obtained for the biopsy must not have been previously irradiated. If a patient does not have any available archival tissue ≤ 1 year old and the treating investigator does not feel that it would be safe to perform a fresh biopsy, the requirement for a fresh biopsy may be waived after discussion with the Principal Investigator. * Written informed consent for screening and trial participation procedures including biological material transfer and handling. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Hematopoietic status: * Absolute neutrophil count ≥ 1.0 × 109/L, * Platelet count ≥ 100 × 109/L, * Hemoglobin ≥ 9 g/dL * Hepatic status: * Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (\< 2 × ULN) is allowed. * AST and ALT ≤ 2.5 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN. * Renal status: * Creatinine ≤ 1.5 ×ULN or creatinine clearance \> 60 ml/min * Proteinuria \< 1 g/day * International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant. * If female of childbearing potential, must have a negative pregnancy test within 7 days of initiating treatment. Childbearing potential is defined by: those who have not been surgically sterilized and/or have had a menstrual period in the past year. * Participants of childbearing potential (as defined above) must be willing to use effective contraception during treatment and up to 7 months after stop of trial treatment. Acceptable methods of contraception are intrauterine devices, bilateral tubal occlusion, vasectomized, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed. * Must not be breastfeeding/lactating. Exclusion Criteria: * Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA4 therapy * Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) * Positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA \[qualitative\]). * History of interstitial lung disease * Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of CNS metastases or spinal cord compression are eligible if they are clinically stable for at least 4 weeks before first dose of investigational product and do not require high-dose steroid treatment). * History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥3), angina, myocardial infarction or ventricular arrhythmia. * Previous severe hypersensitivity reaction to treatment with another monoclonal antibody. * Active infection requiring systemic therapy. * Chronic systemic therapy with immunosuppressive agents including corticosteroids. * Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the trial. * Concurrent disease or condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient's safety. * No uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen. * Chemotherapy, radiotherapy, and/or biological cancer therapy within 3 weeks prior to the first trial dose or has not recovered to CTCAE v.4 grade 1 or better from adverse events (except alopecia). * Unresolved or unstable, serious adverse events from prior administration of another investigational drug. * Live vaccines within 30 days prior to the first dose of trial therapy and during trial treatment.