STEMVAC vaccine plus chemotherapy for PD-L1 negative metastatic triple-negative breast cancer.
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 trial will try giving the STEMVAC cancer vaccine together with standard chemotherapy to adults with PD‑L1 negative metastatic triple‑negative breast cancer to boost the immune system against the tumor.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Washington Academic / other |
| Drugs / interventions | denosumab, chemotherapy, immunotherapy, radiation |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT07078604 on ClinicalTrials.gov |
What this trial studies
This phase II trial combines a plasmid DNA vaccine (STEMVAC) targeting CD105, Yb-1, SOX2, CDH3 and MDM2 with sargramostim as an intradermal adjuvant alongside systemic chemotherapy chosen by the treating oncologist. Participants receive three priming vaccine doses every 21–28 days timed around chemotherapy, two booster doses at months 4 and 7, and further boosters every six months if there is no progression or unacceptable toxicity. Patients undergo imaging (CT or PET), research blood sampling, and optional CT- or ultrasound-guided biopsies during the study, with follow-up visits for three years after treatment. The trial enrolls adults with PD‑L1 negative metastatic triple‑negative breast cancer and ECOG performance status of 0–2.
Who should consider this trial
Good fit: Adults (≥18 years) with histologically confirmed PD‑L1 negative metastatic triple‑negative breast cancer, ECOG ≤2, HER2 negative/low per ASCO/CAP guidelines, who can receive systemic chemotherapy and attend the Seattle treatment site are the intended candidates.
Not a fit: Patients with PD‑L1 positive tumors, poor performance status, uncontrolled medical conditions, inability to travel to the Seattle site, or unwillingness to undergo research biopsies may not benefit from or be eligible for this approach.
Why it matters
Potential benefit: If successful, adding STEMVAC to chemotherapy could strengthen anti-tumor immunity and improve tumor control and progression-free survival for patients with PD‑L1 negative metastatic triple‑negative breast cancer.
How similar studies have performed: Early-phase cancer vaccine trials and vaccine-plus-GM‑CSF combinations have shown immune responses and occasional tumor regressions but have not yet produced consistent, practice-changing results in metastatic triple‑negative breast cancer, so this approach remains experimental.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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 * 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 * Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines and any STEMVAC vaccination * Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine * Any condition that may interfere with the patient's participation in the study per treating physician
Where this trial is running
Seattle, Washington
- Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)
Study contacts
- Principal investigator: Brie Chun, MD — Fred Hutch/University of Washington Cancer Consortium
- Study coordinator: Research Coordinator(s)
- Email: cvitrial@uw.edu
- Phone: 1-866-932-8588
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.