Overview

This phase II trial studies how well a vaccine, STEMVAC, works in combination with standard endocrine-based therapy (ET) or chemotherapy (CDK4/6 inhibitor or capecitabine) in treating patients with hormone receptor (HR) positive, HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that are expressed on breast cancer stem cells, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Standard ET is treatment that adds, blocks, or removes hormones in order to slow or stop the growth of cancer. Standard CDK4/6 inhibitors may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Giving STEMVAC in combination with standard ET or chemotherapy may be an effective treatment for metastatic HR positive, HER2 negative breast cancer.

Eligibility

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