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 fined 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 antibodies/clones in breast cancer at time of eligibility

Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or PET Response Criteria in Solid Tumors (PERCIST). 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

• NOTE: Only chemotherapy partners listed in the protocol are allowed to be administered in metastatic setting concurrently with STEMVAC vaccine

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