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

NCT07078604 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1125414NCI-2025-0432720925
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC): Incidence of patients who develop a positive immunogenic response after vaccination

  The Th1 STEMVAC antigen specific immune response will be determined by IFN-gamma ELISPOT. Magnitude of Th1 response will be defined for each antigen in STEMVAC for each patient as the value of the corrected spots per well (CSPW) (CSPW= \[(mean of spots in the antigen stimulated wells) - (mean of antigens for the no-antigen negative control wells)\] for the same time point). Patients are considered to have preexisting immune response if the mean of spots in antigen wells is greater than the mean + 2 standard deviations of no-antigen wells at baseline. Patients are considered to have generated or enhanced antigen specific immunity post-vaccine if the maximal corrected IFN-gamma response post-vaccine is greater than the mean + 2 standard deviations of the baseline level (p \< 0.05). A patient will be considered an immunogenic responder if they develop an antigen-specific immune response to at least 1 of the 5 vaccine antigens.

  Baseline up to 7 months after STEMVAC priming dose #3

• Incidence of adverse events

  Will be determined by chemical and clinical parameters evaluated at various time points. Toxicity grading will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 6.0 and monitoring of adverse events will be done per Food and Drug Administration and NCI guidelines. Descriptive statistics will be provided on the key demographic and clinical variables, such as mean, standard deviation, and range for continuous variables, and percent and number for categorical variables, such as toxicity grades.

  Up to 21 or 28 days after completion of study treatment

Secondary Outcomes (4)

• 6-month overall response rate

  At 6 months

• Progression-free survival (PFS)

  From the start of treatment to the worsening of cancer or death whichever occurs first, assessed up to 3 years after completion of study treatment

• Overall survival (OS)

  Up to 3 years after completion of study treatment

• Magnitude of immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC)

  Baseline up to 7 months after STEMVAC priming dose #3

Study Arms (1)

Treatment (chemotherapy, STEMVAC, GM-CSF)

EXPERIMENTAL

Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim 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 CT or PET scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.

Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine; Drug: Chemotherapy; Procedure: Computed Tomography; Biological: Sargramostim; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography (PET); Procedure: Image Guided Biopsy

Interventions

CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine BIOLOGICAL

Given ID

Also known as: CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine, STEMVAC, STEMVAC Th1 Polyepitope Plasmid-based Vaccine

Treatment (chemotherapy, STEMVAC, GM-CSF)

Computed Tomography PROCEDURE

Undergo CT scans

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (chemotherapy, STEMVAC, GM-CSF)

Sargramostim BIOLOGICAL

Given ID

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Treatment (chemotherapy, STEMVAC, GM-CSF)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (chemotherapy, STEMVAC, GM-CSF)

Positron Emission Tomography (PET) PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, PET scan, PT

Treatment (chemotherapy, STEMVAC, GM-CSF)

Chemotherapy DRUG

Given standard of care chemotherapy

Treatment (chemotherapy, STEMVAC, GM-CSF)

Image Guided Biopsy PROCEDURE

Undergo image-guided biopsy

Also known as: Image-Guided Biopsy, Imaging for Biopsy, Imaging Guided Biopsy

Treatment (chemotherapy, STEMVAC, GM-CSF)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Kuni Foundation: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Drug Therapy; sargramostim; Colony-Stimulating Factors; Magnetic Resonance Spectroscopy; X-Rays; Image-Guided Biopsy; Biopsy

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Brie Chun, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Coordinator(s)

CONTACT

1-866-932-8588; cvitrial@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 22, 2025
• Study Start: March 24, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)