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

A Multiantigen Vaccine (STEMVAC) for Adjuvant Treatment of Patients With Moderate or Extensive Residual Triple-Negative Breast Cancer

This phase II trial evaluates whether a multi-antigen vaccine called STEMVAC improves disease-free survival after surgery in patients with triple-negative breast cancer (TNBC) and moderate or extensive residual cancer burden. TNBC has an aggressive clinical course and poorer disease-free survival compared to other subtypes. While patients who have no remaining tumor in the breast or lymph nodes after surgery have excellent long-term outcomes, patients with moderate or extensive residual cancer burden remain at high risk for early disease return and poorer prognosis. STEMVAC is designed to target proteins that tumor 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. Giving STEMVAC after surgery may improve disease-free survival rates in TNBC patients with moderate or extensive residual cancer burden.

Study Overview

• Status: Not yet recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Triple-Negative Breast Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine; Drug: Recombinant Granulocyte-Macrophage Colony-Stimulating Factor

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Research Coordinator(s); Phone Number: 866-932-8588; Email: cvitrial@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Natasha Hunter, MD
      • Contact: Research Coordinator(s); Phone Number: 866-932-8588; Email: cvitrial@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (STEMVAC, GM-CSF); Patients receive STEMVAC with 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.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine; Given ID; Other Names: CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine; STEMVAC; STEMVAC Th1 Polyepitope Plasmid-based Vaccine; Drug: Recombinant Granulocyte-Macrophage Colony-Stimulating Factor; Given ID; Other Names: GM-CSF; GM CSF; GMCSF; Colony-Stimulating Factor, Granulocyte-Macrophage; CSF 39300; CSF 39300/GM-CSF; CSF-GM (Hoechst); GM-CSF (Schering); Recombinanr Colony-Stimulating Factor 2; Recombinant Colony-Stimulating Factor 2
Active Comparator: Arm B (GM-CSF); 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.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Recombinant Granulocyte-Macrophage Colony-Stimulating Factor; Given ID; Other Names: GM-CSF; GM CSF; GMCSF; Colony-Stimulating Factor, Granulocyte-Macrophage; CSF 39300; CSF 39300/GM-CSF; CSF-GM (Hoechst); GM-CSF (Schering); Recombinanr Colony-Stimulating Factor 2; Recombinant Colony-Stimulating Factor 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive breast cancer free survival (IBCFS)	Kaplan-Meier curves will be generated with median estimation and 95% confidence interval, and log-rank tests will be conducted to compare the survival difference between groups. Will calculate the 3-year IBCFS rate with a 95% confidence interval from Kaplan-Meier methods using Greenwood standard errors.	Time from randomization to local or distant recurrence or death, assessed up to 3 years
Dynamics and characteristics of circulating tumor deoxyribonucleic acid (ctDNA)	Through serial ctDNA evaluation, each sample will be assessed for ctDNA detectability and, if detectable, total ctDNA mass (continuous variable, as reported by the assay platform) will be calculated. ctDNA detectability and quantitative ctDNA measures will be summarized descriptively by timepoint and study arm, and changes over time will be evaluated using methods appropriate to the final endpoint definition, data distribution, and repeated-measures structure of the data. Associations with IBCFS will also be explored. Copy number variants (including aneuploidy, chromosome-level gains, losses, and amplifications, as defined by the final assay methodology) will also be tracked and tabulated, and changes over time will be evaluated descriptively in both study arms.	Up to 3 weeks after last vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Safety and systemic toxicity will be determined by clinical and laboratory parameters evaluated at protocol-specified time points. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0. The type and grade of toxicities observed during the immunization regimen will be summarized, and the duration of toxicities will be summarized using descriptive statistics. All adverse events reported by the investigator will be tabulated according to the affected body system. The frequency and severity of adverse events will be summarized using proportions and corresponding 95% confidence intervals. Demographic and baseline characteristics obtained at enrollment will be summarized in tabular and/or graphical formats using descriptive statistics.	Up to 3 weeks after last vaccination
Immune response	Immune response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine (STEMVAC) will be measured in peripheral blood functionally by IFN-g enzyme-linked immunosorbent spot, phenotypically using cytometry by time-of-flight to identify T-cell clonal populations, and genomically, using T-cell receptor beta sequencing of CD4+ CD8+ T-cells.	Up to 3 weeks after last vaccination
Expression of epithelial to mesenchymal transformation (EMT)-associated genes	EMT-associated gene expression profiles in residual triple negative breast cancer in surgical pathology samples will be defined for each patient with particular attention on STEMVAC antigen expression. Expression of these EMT-related genes will be assessed using RNA extracted from formalin-fixed paraffin-embedded tissue.	Archival tissue is collected after enrollment, within 30 days of baseline visit

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Natasha Hunter, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): July 16, 2029
• Study Completion (Estimated): July 16, 2030

Study Registration Dates

• First Submitted: July 17, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Biological Factors; Carbohydrates; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Specimen Handling; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors
• Other Study ID Numbers: RG1126489; NCI-2026-04722 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No