A Vaccine (STEMVAC) with Standard Endocrine-Based Therapy or Chemotherapy for the Treatment of Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

Inclusion Criteria

• Patients must be at least ≥ 18 years of age
• Histologically confirmed hormone receptor positive metastatic breast cancer: Tumors that are positive for estrogen receptor (ER) and/or progesterone receptor (PR)
• HER2-negative or HER2-low will be included and defined as: * 0-1+ HER2 expression by immunohistochemistry (IHC) OR * Fluorescence in situ hybridization (FISH) negative OR * HER2 2+ and FISH negative * HER2 low per standard of care in breast cancer
• Patients should be receiving the following therapies to be eligible for the study: * Cohort 1: First or second line of endocrine therapy in combination with a CDK4/6 inhibitor * Cohort 2: Progressed on endocrine-based therapies and after completion of at least 1 cycle of capecitabine
• Subjects with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1
• Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Willing to undergo up to two serial biopsies while on study
• Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. This site should not be a site that is used to determine measurable disease for efficacy purposes. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions
• White blood cell (WBC) ≥ 2500/mm^3 (within 30 days of receiving the study vaccine)
• Lymphocyte count ≥ 500/mm^3 (within 30 days of receiving the study vaccine)
• Absolute neutrophil count (ANC) ≥ 1,000/µL (within 30 days of receiving the study vaccine)
• Platelets ≥ 75,000/µL (within 30 days of receiving the study vaccine)
• 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 30 days of receiving the study vaccine)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN) (within 30 days of receiving the study vaccine)
• Creatinine ≤ 2.0 mg/dL or creatinine clearance > 30 ml/min (within 30 days of receiving the study vaccine)
• Patients of child-bearing potential must agree to use dual methods of contraception and have a negative 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 postmenopausal. Effective methods of contraception must be used throughout the study and until the end of treatment on study
• Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment

Exclusion Criteria

• Patients with any of the following cardiac conditions: * Symptomatic restrictive cardiomyopathy * Dilated cardiomyopathy * Unstable angina within 4 months prior to enrollment * New York Heart Association functional class III-IV heart failure on active treatment * Symptomatic pericardial effusion * Uncontrolled hypertension * Uncontrolled cardiac arrhythmias
• Patients with any autoimmune disease or comorbidities requiring chronic steroids or immunosuppressants
• A non-breast malignancy requiring radiation or systemic therapy within last 5 years
• Known hypersensitivity reaction to the granulocyte-macrophage colony-stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
• Pregnant or breast feeding
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive), or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Major surgery within the 4 weeks prior to initiation of study vaccine
• Current use of immunosuppressive agents or systemic corticosteroids. Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids ≤ 30 days prior to starting study drug will be excluded
• Patient is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug * NOTE: Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed
• Must be 14 days between a non-study and non-live vaccine and any STEMVAC vaccination * Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine
• Any condition that may interfere with the patient’s participation in the study per treating physician