Adoptive T-Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine, Pepinemab and Trastuzumab for the Treatment of HER2 Positive Metastatic Breast Cancer

Inclusion Criteria

• Patients must have a histologically confirmed HER2 positive breast cancer and must be candidates for trastuzumab therapy as per current standard of care. * Note: Human epidermal growth factor receptor (HER2) positive breast cancer is defined by tumor tissue HER2 overexpression and or tumor HER2 amplification per American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) criteria
• Patients will be eligible regardless of estrogen receptor (ER) / progesterone receptor (PR) status which will be determined per 2020 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline and hormonal therapy will be allowed to continue for patients with ER/PR positive disease
• Patients must have evaluable disease, defined as at least one lesion that can be accurately measured >= 10 mm by standard imaging techniques that can be include but not limited to computerized tomography (CT), positron emission tomography (PET), PET/CT, magnetic resonance imaging (MRI). Skeletal disease which is measurable by PET/CT or bone scan will also be allowed
• Patients must have had disease progression while on trastuzumab for the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) and received no more than 3 lines of cytotoxic chemotherapy in the setting of metastatic disease
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count (ANC) >= 1500/ uL (within 14 days of registration)
• Hemoglobin >= 9.0 g/dL (within 14 days of registration)
• Platelets >= 75 000/ uL (within 14 days of registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert’s syndrome in whom total bilirubin must be < 3.0 mg/dL (within 14 days of registration)
• Aspartate aminotransferase (AST)/alanine aminotransaminase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 14 days of registration)
• Creatinine =< 1.5 x institutional upper limit of normal (ULN) (within 14 days of registration)
• Partial thromboplastin time (PTT)/international normalized ratio (INR) =< 1.5 of upper limits of normal (ULN), unless on a therapeutic anticoagulant (within 14 days of registration)
• Left ventricular ejection fraction above institutional lower limit of normal (by echocardiogram or multigated acquisition scan (MUGA) scan (within 14 days of registration)
• Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum or urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose. To be considered of not to be of childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (not in the setting of post chemotherapy) or patients must be surgically sterile.
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
• Patients must have a life expectancy of at least 12 weeks

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 14 days prior to beginning protocol therapy
• Patients may not be receiving any other investigational agents within 14 days or 5 half-lives (whichever is longer) prior to beginning protocol therapy.
• Patients with uncontrolled brain metastases or leptomeningeal disease
• 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 with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded
• Female patients who are pregnant or nursing are not eligible
• Second invasive malignancy requiring active treatment
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) is not permitted
• Any known positive test for Hepatitis B or Hepatitis C virus indicating acute or chronic infection is not permitted
• Patients who have received a live attenuated vaccine =< 30 days of registration are not eligible
• Patients not able to comply with the treatment schedule and study procedures for any reason are not eligible
• Patients previously treated with any form of adoptive cell transfer therapy