Cancer Vaccine for Breast Cancer

Overseen By Mary Disis

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Washington

Must be taking: Bisphosphonates, Denosumab, Endocrine therapy

Disqualifiers: Cardiac conditions, Seizure disorder, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 months

42 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be at least 28 days post chemotherapy, monoclonal antibody therapy, and systemic steroids before enrolling. You can continue taking bisphosphonates, denosumab, and/or endocrine therapy.

What data supports the effectiveness of the treatment CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine for breast cancer?

Research shows that DNA vaccines targeting specific cancer antigens can trigger strong immune responses, as seen with a similar vaccine for glioma that induced protective and therapeutic effects. Additionally, DNA vaccines targeting HER2 in breast cancer have shown promising immune responses, suggesting potential effectiveness for the CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope vaccine. ^{1 2 3 4 5}

What makes the STEMVAC treatment unique for breast cancer?

The STEMVAC treatment is unique because it is a DNA vaccine designed to trigger the immune system to specifically target and destroy breast cancer cells by recognizing multiple cancer-specific proteins. This approach aims to provide a more targeted and long-lasting immune response compared to traditional treatments. ^{1 2 4 5 6}

What is the purpose of this trial?

This trial tests a new DNA-based vaccine for patients with advanced breast cancer that doesn't respond well to chemotherapy. The vaccine aims to help the immune system target and destroy cancer cells. Patients receive different doses of the vaccine to find the best one, and their health is monitored over time. DNA vaccination has emerged as an attractive immunotherapeutic approach against cancer due to its simplicity, stability, and safety.

Research Team

Mary L. Disis

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with HER2-negative stage III-IV breast cancer who have completed standard treatments and are not currently pregnant or breastfeeding. They should have a life expectancy over 6 months, normal organ function tests, no recent major illnesses or surgeries, and agree to use contraception. Those with autoimmune diseases, seizure disorders, significant heart conditions, or on other treatment studies can't join.

Inclusion Criteria

I've finished my standard treatment and have little to no side effects.

I have stage III-IV HER2 negative breast cancer with no signs of the disease or only stable bone disease.

I am currently taking bisphosphonates, denosumab, or hormone therapy.

Exclusion Criteria

I have an autoimmune disease that isn't managed well, even with treatment.

I am at risk for stomach bleeding due to ulcers or long-term use of NSAIDs.

I am allergic or cannot take rhuGM-CSF based products.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the STEMVAC vaccine with rhuGM-CSF intradermally every 28 days for 3 months. Booster vaccines may be given at 3 and 9 months after the third vaccine.

3 months

1-3 injections every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits twice yearly.

Up to 5 years

2 visits per year

Treatment Details

Interventions

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

Trial Overview The trial is testing a new DNA vaccine targeting proteins in breast cancer stem cells that resist chemotherapy and spread the disease. It aims to teach the body's immune system to destroy these tumor cells. The study will determine the safest dose of this vaccine while monitoring its effects through lab analysis.

Participant Groups

Group I: Arm 4 (STEMVAC) Experimental Treatment 2 Interventions

Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Group II: Arm 3 (STEMVAC) Experimental Treatment 2 Interventions

Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Group III: Arm 2 (STEMVAC) Experimental Treatment 2 Interventions

Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Group IV: Arm 1 (STEMVAC) Experimental Treatment 2 Interventions

Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 1 injection ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine is already approved in United States for the following indications:

Approved in United States as STEMVAC for:

• Triple Negative Breast Cancer
• Non-Small Cell Lung Cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Breast Cancer Alliance

Collaborator

Trials

1

Recruited

40+

Breast Cancer Alliance

Collaborator

Trials

2

Recruited

100+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

A novel polyepitope DNA vaccine targeting breast cancer-specific antigens HER2 and Mammaglobin-1 was developed, showing potential for inducing a T-cell-mediated immune response to selectively eliminate tumor cells.

The vaccine was successfully delivered into dendritic cells, which are crucial for initiating immune responses, and the expression of the target antigens was confirmed, indicating the vaccine's potential effectiveness in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of Polyepitope DNA Vaccine against Breast Carcinoma Cells and Analysis of Its Expression in Dendritic Cells. Nazarkina, ZhK., Khar'kova, MV., Antonets, DV., et al.[2016]

Vaccination with a plasmid DNA encoding the SOX6 protein successfully generated specific cytotoxic T-lymphocyte (CTL) responses in glioma-bearing mice, indicating its potential as an effective immunotherapy target.

The SOX6-DNA vaccine demonstrated both protective and therapeutic antitumor effects, which were dependent on the presence of CD4 and CD8 T cells, highlighting the importance of these immune cells in combating glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6. Ueda, R., Kinoshita, E., Ito, R., et al.[2016]

The study developed a novel DNA vaccine (pScFvDEC-MeHer2) targeting HER2 overexpression in breast cancer, which showed a strong immune response in mice, including significant increases in IgG and IFN-γ levels.

The pScFvDEC-MeHer2 vaccine was more effective than the standard pMeHer2 vaccine in eliciting T-cell responses, indicating its potential as a promising candidate for further research in HER2-positive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205. Gül, A., Döşkaya, M., Can, H., et al.[2022]

DNA-based cancer vaccines can effectively induce immunity against tumor-associated antigens (TAAs) by delivering a recombinant plasmid that produces multiple epitopes, which are then presented to CD8+ T-lymphocytes.

This polyepitope approach allows for a broader immune response by including various immunogenic epitopes and accommodating patients with different MHC haplotypes, potentially enhancing the vaccine's effectiveness across diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TAA polyepitope DNA-based vaccines: a potential tool for cancer therapy. Bei, R., Scardino, A.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Design of Polyepitope DNA Vaccine against Breast Carcinoma Cells and Analysis of Its Expression in Dendritic Cells. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6. [2016]

3. England pubmed.ncbi.nlm.nih.gov

An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A novel DNA vaccine encoding PDGFRbeta suppresses growth and dissemination of murine colon, lung and breast carcinoma. [2009]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

TAA polyepitope DNA-based vaccines: a potential tool for cancer therapy. [2021]