A Cancer Vaccine (STEMVAC) in Combination With Chemotherapy for the Treatment of PD-L1 Negative Metastatic Triple-Negative Breast Cancer

A Phase II Trial of the Immunogenicity of a DNA Plasmid-Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDH3, CD105) in Patients With Metastatic Triple-Negative Breast Cancer

This phase II trial studies how well a cancer vaccine called STEMVAC works in combination with chemotherapy in treating patients with PD-L1 negative, triple-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. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving STEMVAC in combination with chemotherapy may be an effective treatment for PD-L1 negative metastatic triple-negative breast cancer.

OUTLINE:

Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim intradermally (ID) every 21-28 days (7-13 days after each chemotherapy administration or during the off week of weekly chemotherapy), 2 booster STEMVAC/sargramostim doses at 4 and 7 months after 3rd priming dose, and then every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo image-guided biopsy, for research purposes, on study, as well as computed tomography (CT) or positron emission tomography (PET) scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.

After completion of study treatment, patients are followed up at 21 or 28 days and then every 6 months for 3 years.

Inclusion Criteria:

• Patients must be at least ≥ 18 years of age

  • Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients < 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable

• Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2

• Histologically confirmed triple-negative breast cancer

  • Tumors with estrogen receptor (ER)-low (≤ 5%) or negative and progesterone receptor (PR)-low (≤ 5%) or negative will be included
  • HER2-negative or HER2-low will be defined by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2023 "Human Epidermal Growth Factor Receptor 2 (HER2) Breast Testing Guideline Update" which reaffirms the 2018 "HER2 Breast Testing Guideline Focused Update"

• Tumor is negative for PD-L1 marker testing per standard of care immunohistochemistry 22C3 pharmDx assay

• 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

• Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions

• Patients can not have received any prior cancer immunotherapy in the metastatic setting

• Prior Food and Drug Administration (FDA)-approved antibody drug conjugates are allowed

• Patients are appropriate candidates to receive standard of care chemotherapy as per treating oncologist's clinical judgement

• Patients who have received prior neoadjuvant or adjuvant chemotherapy are allowed

• A minimum of 14 days washout since last systemic therapy or any palliative radiotherapy is required

• Treatment with a bisphosphate or denosumab concurrently with protocol-specific therapy is allowed while on study (it is not exclusionary)

• Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions

• 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

• Willing to undergo up to two serial biopsies while on study

• White blood cell (WBC) ≥ 2.5 THOU/uL (Within 28 days of receiving first study vaccine)

• Lymphocyte count ≥ 0.5 THOU/uL (Within 28 days of receiving first study vaccine)

• Absolute neutrophil count (ANC) ≥ 1.0 THOU/uL (Within 28 days of receiving first study vaccine)

• Hemoglobin (Hgb) ≥ 9 g/dL (Within 28 days of receiving first study vaccine)

• Platelets ≥ 75 THOU/uL (Within 28 days of receiving first 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/d (Within 28 days of receiving first study vaccine)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (Within 28 days of receiving first study vaccine)

• Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance > 60 mL/min (Within 28 days of receiving first 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 person of child-bearing potential. Acceptable methods of contraception are abstinence, 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. Effective methods of contraception must be used throughout the study until the end of treatment on study

Exclusion Criteria:

• Patient has received more than one line of prior therapy in metastatic setting

• Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay

• Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed. Participation in a trial for chimeric antigen receptor (CAR)-T cell therapy may be permitted if the CAR-T cell therapy is not planned to occur until after the currently proposed treatment (i.e. no longer participating in STEMVAC and chemotherapy trial)

• 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

• Patients with any autoimmune disease or comorbidities that require chronic systemic steroids or immunosuppressants. Patients with conditions requiring inhaled, intranasal or topical steroids are permitted

• Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF

• A non-breast malignancy requiring radiation or systemic therapy within last 5 years or any B-cell malignancy (e.g., chronic lymphocytic leukemia or follicular lymphoma) under active surveillance

• Pregnant and breastfeeding individuals

• 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

• Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines 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