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.
• 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. 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
• Patients should 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) ≥ 2500/mm\^3 (Within 28 days of receiving first study vaccine)
• Lymphocyte count ≥ 500/mm\^3 (Within 28 days of receiving first study vaccine)
• Absolute neutrophil count (ANC) ≥ 1000/μL (Within 28 days of receiving first study vaccine)
• Hemoglobin (Hgb) ≥ 9 g/dL (Within 28 days of receiving first study vaccine)
• Platelets ≥ 75,000/μL (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/dL (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