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

A Phase II Study of STEMVAC Vaccine Therapy for Patients With Hormone Receptor Positive Metastatic Breast Cancer

This phase II trial studies how well a vaccine, STEMVAC, works in combination with standard endocrine-based therapy (ET) with a CDK4/6 targeted drug therapy, or with the chemotherapy drug 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 cancer cells use when they become more aggressive and start to spread, 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, including abemaciclib, 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.

OUTLINE: Patients with ET-sensitive disease are assigned to Cohort 1, while patients with ET-resistant disease are assigned to Cohort 2.

COHORT 1: After completion of 2 cycles of standard of care (SOC) ET + CDK4/6 inhibitor (CDK4/6i) therapy or abemaciclib alone, patients receive STEMVAC intradermally (ID) on the following schedule: 1) Three "priming" doses every 28 days; 2) Two "booster" doses at 6 and 9 months after "priming" dose #1; and 3) Additional "booster" doses every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo image-guided biopsies for research purposes, as well as collection of blood samples and computed tomography (CT) or positron emission tomography (PET) scans throughout the trial.

COHORT 2: After completion of 1 cycle of SOC capecitabine treatment, patients receive STEMVAC ID on the following schedule: 1) Three "priming" doses every 28 days; 2) Two "booster" doses at 6 and 9 months after "priming" dose #1; and 3) Additional "booster" doses every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo image-guided biopsies for research purposes, collection of blood samples, and fluoroestradiol (FES) positron emission tomography (PET) scans, as well as CT or PET scans throughout the trial.

After completion of study treatment, patients are followed every 6 months for 3 years.

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 the metastatic setting, in combination with a CDK4/6 inhibitor. Patients must have completed at least 2 cycles of CDK4/6 inhibitor. Patients who have stopped endocrine therapy for intolerance but remain on abemaciclib monotherapy will be considered for enrollment at the PI's discretion
  • 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

• 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

• White blood cell (WBC) ≥ 2000/mm^3 (within 28 days of receiving the study vaccine)

• Lymphocyte count ≥ 500/mm^3 (within 28 days of receiving the study vaccine)

• Absolute neutrophil count (ANC) ≥ 800/µL (within 28 days of receiving the study vaccine)

• Platelets ≥ 75,000/µL (within 28 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 28 days of receiving the study vaccine)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN) (within 28 days of receiving the study vaccine)

• Creatinine ≤ 2.0 mg/dL or creatinine clearance > 30 mL/min (within 28 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/comorbidity that require 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, and 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 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 oncologist