A Vaccine (STEMVAC) for Improving Survival in Patients With Triple-Negative Breast Cancer and Moderate or Extensive Residual Cancer Burden

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid (DNA) vaccine (STEMVAC) with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) intradermally (ID) every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.

ARM B: Patients receive GM-CSF ID every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up at 3 weeks after their last vaccination and then every 6 months for 3 years.

Inclusion criteria

• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2
• Triple-negative breast cancer as determined by the treating oncologist
• Completed standard of care neoadjuvant chemotherapy in the opinion of their treating oncologist
• Patients whose tumors progress on neoadjuvant therapy may be enrolled
• No clinical evidence of local or distant recurrence
• Plan to receive standard of care adjuvant directed therapy
• Completed standard of care locoregional treatment, including definitive breast and lymph node surgery followed by standard radiation therapy, if recommended
• Residual cancer burden (RCB) index 2 or 3 as calculated per routine anatomic pathology clinical standards
• Absolute neutrophil count (ANC) ≥ 800/μL (within 30 days of first study vaccine administration)
• Hemoglobin (Hgb) ≥ 8 g/dL (within 30 days of first study vaccine administration)
• Platelets ≥ 75,000/ μL (within 30 days of first study vaccine administration)
• 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 first study vaccine administration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (within 30 days of first study vaccine administration)
• Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance > 60 mL/min (within 30 days of first study vaccine administration)
• At least 28 days post systemic steroids prior to enrollment, unless used as part of prophylaxis to prevent intravenous (IV) contrast reactions.

• Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed
• 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
• 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

Exclusion criteria

• Toxicities related to prior exposure to immune checkpoint inhibitors for which immune checkpoint inhibitors cannot be safely continued as determined by study investigator
• Germline BRCA1 or BRCA2 mutations with adjuvant olaparib planned within the study period

• NOTE: If olaparib is not planned, then these patients are eligible
• Any known 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
• Autoimmune disease requiring active systemic treatment
• Known hypersensitivity reaction to the 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] is detected)
• Major surgery within the 4 weeks prior to initiation of first study vaccine
• Enrollment in any other clinical protocol or investigational trial that involves concurrent administration of experimental therapy and/or therapeutic devices, or investigational drug. Patients who completed prior clinical trials (such as neoadjuvant treatment, surgery or radiation trials) and are on long term follow up are permitted