A Specialized Type of Immune Cells (HER2Bi-Armed Activated T Cells) and Pembrolizumab in Treating Patients with Metastatic Breast Cancer

Inclusion Criteria

• Histologically confirmed breast cancer (infiltrating ductal or lobular breast carcinoma) with evidence of measurable metastatic disease; metastatic disease must be biopsy proven * Since histologic type, lymphatic permeation, blood vessel invasion, and degree of anaplasia may be prognostic variables, appropriate slides of the primary lesion will be requested for future review; HER2, estrogen, and progesterone receptor positivity will be recorded
• Measurable lesion; patients are required to have at least one measurable non-bone lesion >= 10 mm that has not been irradiated * Measurable metastatic disease documented by radiograph, computed tomography (CT) scan, positron emission tomography (PET)/CT, magnetic resonance imaging (MRI), or physical exam is required; each subject will be required to have at least one measurable lesion that has not been irradiated with a minimum size in at least one diameter of >= 10 mm for liver lesions, lung, skin, and >= 15 mm lymph node metastases; biopsy of recurrent site(s) is not required
• Patients must have HER2 status determined by chromogenic in situ hybridization (CISH), fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC); HER2 status of positive or negative are both eligible for the study
• Be female >=18 years of age
• Be willing and able to provide written informed consent for the trial
• Have a life expectancy >= 3 months
• Have a performance status (PS) Eastern Cooperative Oncology Group (ECOG) 0-1
• Absolute lymphocyte count >= 500/mm^3 (within 10 days prior to on-study date)
• Absolute neutrophil count (ANC) >= 1,500/mcL (within 10 days prior to on-study date)
• Platelets >= 100,000/mcL (within 10 days prior to on-study date) Note: If there is an absence of other medical conditions related to thrombocytopenia that would preclude participation in the protocol as determined by the treating investigator, the platelet requirement is >= 75,000 / mcL
• Hemoglobin >=9 g/dL (within 10 days prior to on-study date) (or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (within 10 days prior to on-study date)
• Serum total bilirubin =< 1.5 x ULN (within 10 days prior to on-study date) OR
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases (within 10 days prior to on-study date)
• Albumin >= 2.5 mg/dL (within 10 days prior to on-study date)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to on-study date)
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 10 days prior to on-study date)
• Female patients of childbearing potential should have a negative pregnancy test within 10 days prior to on-study date; if a urine or serum test is positive or cannot be confirmed as negative, the other (urine or serum pregnancy test, whichever was not performed first) will be required
• Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication
• Patients must have had two or more lines of prior therapy (chemo or hormonal) in the metastatic setting

Exclusion Criteria

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to on-study date
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to PBZ or any of its excipients
• Lack of recovery (i.e., =< grade 1 or baseline prior to last line of cancer therapy) from non-laboratory adverse events except =< grade 2 neuropathy
• Has history of another malignancy within the past 5 years; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to on-study date and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to leukapheresis; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (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 not considered a form of systemic treatment
• Has a known history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); note: patients may be eligible if HCV antibody is detected as long as HCV viral load is undetectable following a Food and Drug Administration (FDA) approved treatment regimen
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to on-study date. Administration of killed vaccines is allowed * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• Has a history of significant cardiac disease, including: * History of a recent myocardial infarction (within one year), a past myocardial infarction (more than one year ago) along with current coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by multigated acquisition [MUGA] or echocardiogram [ECHO]) * Current history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO) * Clinical evidence of congestive heart failure requiring medical management (irrespective of ECHO results)
• Patient (Pt) may be excluded if, in the opinion of the principal investigator (PI) and investigator team, the pt is not capable of being compliant