DNA vaccine for early stage 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, CDC25B, CD105) in Participants With Early Stage Triple Negative Breast Cancer

This study is testing a new DNA vaccine to see if it can help people with early-stage triple negative breast cancer by boosting their immune system to fight the cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Drugs / interventions: denosumab, methotrexate
• Locations: 3 sites (Baltimore, Maryland and 2 other locations)
• Trial ID: NCT05455658 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effects of a DNA plasmid-based vaccine called STEMVAC in patients with early-stage triple negative breast cancer. The vaccine aims to stimulate the immune system to recognize and attack cancer cells by targeting specific proteins expressed on these cells. Participants will receive the vaccine along with sargramostim, an immune booster, through intradermal injections over a period of several months, followed by booster doses. The study will monitor the immune response and patient outcomes over a five-year follow-up period.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with early-stage triple negative breast cancer (stages IB to III) who have completed standard treatments.

Not a fit: Patients with hormone receptor-positive breast cancer or those who have not completed standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance the immune response against triple negative breast cancer, potentially improving patient outcomes.

How similar studies have performed: While there have been studies exploring immune-based therapies for breast cancer, the specific use of STEMVAC in this context is novel.

Eligibility criteria

Inclusion Criteria:

* Participants with triple negative breast cancer, stages IB, II or III. Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative is defined as breast cancer with less than 10% of ER or PR expression. HER2 negative is defined as:

  * 0-1+ HER2 expression by immunohistochemistry (IHC) OR
  * Fluorescence in situ hybridization (FISH) negative OR
  * HER2 2+ and FISH negative
  * Note: Participants with low ER positivity (≤10%) who are already on adjuvant hormonal therapy will be allowed on study and can continue their adjuvant hormonal treatment during study participation.
* Participants must have completed all standard of care (or investigational) systemic therapy (including immune modulating agents) and radiotherapy if used between 28 and 365 days prior to enrollment

  \* Note: Treatment with a bisphosphonate or denosumab to prevent bone loss is not considered to be systemic therapy for breast cancer and its use within the 28 day pre-enrollment period or while on study is not exclusionary. Treatment with adjuvant olaparib within the 28 day pre-enrollment period or while on study is not exclusionary.
* Participants must agree to avoid systemic steroids for the duration of the treatment period and until completion of the 1 month post 2nd booster vaccine visit (end of treatment)
* Participants 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 participants \< 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable.
* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1
* White blood cell (WBC) \>= 3000/mm\^3 (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* Lymphocyte count \>= 800/mm\^3 (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* Platelet count \>= 100,000/mm\^3 (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* Hemoglobin (Hgb) \>= 10 g/dl (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* Serum creatinine =\< 1.2 mg/dl OR creatinine clearance \> 60 ml/min (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* Total bilirubin =\< 1.5 X upper limit of institutional normal (ULN) (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* AST (aspartate aminotransferase)/serum glutamic-oxaloacetic transaminase (SGOT) =\< 1.5 X upper limit of institutional normal (ULN) (within 60 days of enrollment and at least 28 days post standard of care \[SOC\] treatment)
* 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
* The effects of STEMVAC on the developing human fetus are unknown. For this reason,

  * Female participant agrees to use adequate contraception (examples include: estrogen and/or progestogen containing hormonal contraception, barrier method (condom, cervical cap) or abstinence) while on the study and until 1 month after the 2nd booster vaccination when/if engaging in sex that could lead to pregnancy. Exceptions: Females who have had a hysterectomy, tubal ligation or bilateral oophorectomy OR meet one of the following criteria for postmenopausal: Age \> 60 or age \< 60 with \>= 12 months amenorrhea and follicle-stimulating hormone (FSH) within the testing facility's postmenopausal range
  * Female participant agrees to inform her study physician immediately should she become pregnant or suspect she is pregnant while participating in this study
  * Male participants who are having sex that can lead to pregnancy must use an acceptable form of contraception (vasectomy with the absence of sperm, sexual abstinence, condoms) throughout the course of the study
  * Must be 14 days between a vaccine (i.e. COVID19, Flu, shingrix, Tdap, etc.) and any STEMVAC vaccination. \*\*Note: This does not apply to the Td vaccine.
* Patients must be willing to not undergo major elective surgical procedures with general anesthesia or conscious sedation through the end of treatment visit. (Note: port removal is allowable)
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Contraindication or known hypersensitivity to receiving sargramostim (rhuGM-CSF) or other products
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to STEMVAC
* Participants receiving any other investigational agents
* Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is prohibited during the treatment period of the study, except when taken as low-dose (81 mg) aspirin therapy. Prohibited chronic use is defined as daily use for more than 7 days
* Participants with any clinically significant autoimmune disease uncontrolled with treatment
* Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant and breastfeeding women are excluded from this study
* Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

  \* Note: These individuals are excluded in order to avoid confounding an existing condition with an immune response to STEMVAC
* Chronic usage of immunosuppressants and glucocorticoids (methotrexate for RA, etc.)
* History of invasive breast cancer prior to TNBC diagnosis \* Note: Prior DCIS is allowable

Where this trial is running

Baltimore, Maryland and 2 other locations

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore, Maryland, United States (Active_not_recruiting)
• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)
• University of Wisconsin Carbone Cancer Center — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Mary Disis, MD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Kim Mast

Conditions Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8