Cancer Vaccine for Triple Negative Breast Cancer

Not currently recruiting at 2 trial locations

Overseen By Jennifer Childs, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: NSAIDs, Immunosuppressants, Glucocorticoids

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new cancer vaccine called STEMVAC (CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine) for individuals with stage IB-III triple negative breast cancer. The vaccine boosts the immune system to recognize and destroy cancer cells. Participants will receive the vaccine along with an additional substance to enhance its effects. This trial suits those who have completed their main cancer treatments and have been free from major health issues or surgeries recently. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Do I need to stop my current medications for the trial?

The trial does not specify that you need to stop all current medications, but you must avoid systemic steroids and chronic use of NSAIDs (except low-dose aspirin) during the treatment period. If you are on adjuvant hormonal therapy, you can continue it during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that plasmid DNA vaccines like STEMVAC are generally safe in early studies, meaning patients usually tolerate them well. Previous research has shown that these vaccines trigger immune responses without causing serious side effects. Although the safety of these vaccines in humans is still under study, the current phase of the trial indicates that STEMVAC has passed initial safety tests. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The new cancer vaccine for triple-negative breast cancer is turning heads because it targets multiple tumor antigens using a CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA. This makes it different from standard treatments like chemotherapy, which often target rapidly dividing cells non-specifically. Researchers are particularly excited because this vaccine is designed to train the immune system to recognize and attack cancer cells more precisely, potentially improving effectiveness and reducing side effects. Plus, the inclusion of sargramostim is believed to boost the immune response, offering hope for more durable protection against cancer recurrence.

What evidence suggests that this treatment might be an effective treatment for triple negative breast cancer?

Research has shown that STEMVAC, a DNA-based vaccine, might help the immune system combat triple-negative breast cancer. Studies have found that it targets specific proteins on cancer cells, signaling the immune system to attack them. In this trial, participants will receive the STEMVAC vaccine alongside sargramostim. Early results suggest that combining STEMVAC with chemotherapy could be effective for certain breast cancers, such as PD-L1 negative metastatic triple-negative breast cancer. While researchers continue to gather data, boosting the immune system to recognize cancer cells appears promising. ^{1 3 6 7 8}

Who Is on the Research Team?

Howard Bailey, MD

Principal Investigator

University of Wisconsin, Madison

Mary L. Disis

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with stage IB-III triple negative breast cancer who have finished standard treatments between 28 and 365 days before joining. They must be in good health, not pregnant or breastfeeding, agree to use contraception, and not have HIV, hepatitis B/C, severe allergies to the vaccine components or yeast-based products. Participants can't take chronic NSAIDs except low-dose aspirin.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My kidney function is normal, based on recent tests.

I have recovered from major infections or surgeries and don't have other serious illnesses that would prevent me from following the treatment plan.

Exclusion Criteria

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

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

I do not use NSAIDs daily for more than a week, except for low-dose aspirin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive STEMVAC vaccine with sargramostim intradermally every month for 3 months, followed by booster injections 3 months after the 3rd vaccination and 6 months after the 1st booster

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annually

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The trial tests STEMVAC, a DNA plasmid-based vaccine designed to stimulate the immune system against proteins found on breast cancer cells. It's given alongside Sargramostim which may help boost the body's response to the vaccine.

How Is the Trial Designed?

Group I: Prevention (STEMVAC vaccine, sargramostim) Experimental Treatment 2 Interventions

Patients receive STEMVAC vaccine with sargramostim ID every month for 3 months in the absence of disease progression or unacceptable toxicity. Patients then receive STEMVAC vaccine with sargramostim ID booster injections 3 months after the 3rd vaccination and 6 months after the 1st booster vaccination.

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

In a phase II study involving 14 patients with advanced metastatic triple-negative breast cancer, a 6-week mixed 19-peptide cancer vaccine showed no severe adverse events, indicating a favorable safety profile.

The study found that an increase in peptide-specific IgG correlated with improved overall survival, with a median overall survival of 11.5 months for all patients and 24.4 months for those who completed the vaccination, suggesting potential efficacy of the vaccine in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer. Toh, U., Sakurai, S., Saku, S., et al.[2021]

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]

The multi-peptide TOP2A vaccine effectively stimulates a strong immune response in mice, leading to significant production of Th1 cytokines, which are important for fighting tumors.

In mouse models of triple-negative breast cancer (TNBC), the vaccine not only reduced tumor growth but also decreased tumor incidence and volume, demonstrating its potential as a preventive and therapeutic strategy against this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Striking efficacy of a vaccine targeting TOP2A for triple-negative breast cancer immunoprevention. Lee, SB., Pan, J., Xiong, D., et al.[2023]

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]

A novel DNA vaccine targeting the MYB oncoprotein in colorectal cancer (CRC) was developed, showing potential to elicit a specific immune response against tumors expressing MYB, which is crucial for tumor cell survival.

Combining the vaccine with low-dose cyclophosphamide and anti-PD-1 antibodies enhanced its efficacy, demonstrating that this approach can improve tumor-specific cell killing and provide better protection against aggressive cancer cell lines in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic DNA vaccination against colorectal cancer by targeting the MYB oncoprotein. Cross, RS., Malaterre, J., Davenport, AJ., et al.[2021]

In a study of 83 patients with triple negative breast cancer (TNBC), over 66% exhibited a basal-like immunophenotype, and specific cancer test antigens (CTAs) like MAGE-A1 were frequently expressed, indicating potential targets for immunotherapy.

A significant correlation was found between the expression of CTAs (MAGE-A10 and NY-ESO) and the topoisomerase 2-alpha (TOPO2A) protein, suggesting that combining therapies targeting these markers could be a promising approach for treating TNBC, which currently has limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas. Mrklić, I., Spagnoli, GC., Juretić, A., et al.[2017]

Neoadjuvant immunotherapy, specifically the in situ immunomodulation (neo-ISIM) regimen, effectively generates tumor-specific CD8+ T cells that help control distant metastases and improve survival in mouse models of triple-negative breast cancer.

The success of neo-ISIM relies on the activation of Batf3-dependent dendritic cells and is enhanced by combining it with PD-L1 blockade, indicating a promising multimodal approach for treating high-risk resectable tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant In Situ Immunomodulation Enhances Systemic Antitumor Immunity against Highly Metastatic Tumors. Oba, T., Kajihara, R., Yokoi, T., et al.[2022]

The ImmunoBody vaccine targeting the helicase antigen (HAGE) in triple-negative breast cancer (TNBC) has shown superior T-cell responses compared to traditional peptide immunization, indicating its potential as an effective immunotherapy.

In preclinical models, the ImmunoBody-HAGE vaccine not only generated specific immune responses but also effectively recognized and targeted HAGE-expressing tumor cells, suggesting a promising approach for enhancing treatment outcomes in TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helicase antigen (HAGE)-derived vaccines induce immunity to HAGE and ImmunoBody®-HAGE DNA vaccine delays the growth and metastasis of HAGE-expressing tumors in vivo. Nagarajan, D., Pearson, J., Brentville, V., et al.[2022]

The DKK1-DNA vaccine effectively protects against the development of myeloma and can also treat established myeloma in a mouse model, demonstrating its potential as a therapeutic vaccine.

Combining the DKK1 vaccine with adjuvants like CpG or immune-modulating antibodies significantly enhances its therapeutic effects by promoting strong immune responses and reducing regulatory T cells that suppress immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma. Qian, J., Zheng, Y., Zheng, C., et al.[2021]

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]

Plasmid DNA vaccination targeting tumor mutation-derived neoepitopes successfully induced long-lasting anti-tumor immunity in murine models (CT26 and B16F10), demonstrating the potential for personalized cancer immunotherapy.

The study found that effective tumor growth inhibition required the activation of both CD4+ and CD8+ T cells, and combining DNA vaccination with immune checkpoint inhibitors resulted in enhanced anti-tumor effects compared to either treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA based neoepitope vaccination induces tumor control in syngeneic mouse models. Viborg, N., Pavlidis, MA., Barrio-Calvo, M., et al.[2023]

A novel therapeutic vaccination strategy targeting cancer stem cells (CSCs) in melanoma was developed using synthetic high-density lipoprotein (sHDL) nanodiscs containing peptides from CSC-associated transcription factors, which successfully reduced the frequency of CSCs and promoted effective T cell responses.

This vaccination approach not only inhibited tumor growth and extended survival in animal models but also showed no toxicity to normal stem cells, indicating a safe and potentially versatile treatment for melanoma and other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer stem cell antigen nanodisc cocktail elicits anti-tumor immune responses in melanoma. Aikins, ME., Qin, Y., Dobson, HE., et al.[2023]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05455658

NCT05455658 | STEMVAC in Patients With Early Stage ... This phase II trial studies the effect of DNA plasmid based vaccine (STEMVAC) in treating patients with patients with stage IB-III triple negative breast ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07078604

NCT07078604 | A Cancer Vaccine (STEMVAC) in ... Giving STEMVAC in combination with chemotherapy may be an effective treatment for PD-L1 negative metastatic triple-negative breast cancer. Detailed Description.

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/cd105-yb-1-sox2-cdh3-mdm2-polyepitope-plasmid-dna-vaccine

Clinical Trials Using CD105/Yb-1/SOX2/CDH3/MDM2- ... A Cancer Vaccine (STEMVAC) in Combination with Chemotherapy for the Treatment of PD-L1 Negative Metastatic Triple-Negative Breast Cancer. Status: Approved.

4. link.springer.com link.springer.com/article/10.1007/s12609-024-00552-3

New Vaccine Therapy for Triple-Negative Breast Cancer The objective of this review is to provide an analysis of early-phase clinical trials investigating vaccine therapies for triple-negative breast cancer (TNBC).

5. uwcvi.org uwcvi.org/current-clinical-trials

Clinical Trial Opportunities ... Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDH3, CD105) in Patients with Triple Negative Breast Cancer+C17. Results Summary. Not Accepting Patients. A Phase II ...

6. prevention.cancer.gov prevention.cancer.gov/clinical-trials/clinical-trials-search/nct05455658

STEMVAC in Patients With Early Stage Triple Negative Breast ... This phase II trial studies the effect of DNA plasmid based vaccine (STEMVAC) in treating patients with patients with stage IB-III triple negative breast ...

7. app.emergingmed.com app.emergingmed.com/emed/trial/85893

Vaccine Therapy in Treating Patients With HER2-Negative ... 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10251337/

The future of cancer immunotherapy: DNA vaccines ... Plasmid DNA immunizations have shown a favorable safety profile and there occurs induction of generalized as well as tailored immune responses in preclinical ...