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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer vaccine for treating advanced breast cancer that doesn't respond to certain therapies (HER2-negative stage III-IV). The goal is to determine the best dose and understand any side effects of this DNA-based vaccine, which could help the immune system target and destroy cancer cells. Participants might receive different doses to identify the most effective one. Those with HER2-negative breast cancer that is stable or in remission after standard treatments may be suitable for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

Research shows that the STEMVAC vaccine, targeting breast cancer, has been tested in patients with various types of this disease. In these studies, patients received the vaccine to assess its tolerance and side effects.

The vaccine is administered with rhuGM-CSF, a substance that boosts the immune system. Previous studies found that STEMVAC was generally well-tolerated. Most side effects were mild, such as redness or swelling at the injection site, with some patients reporting fatigue or mild flu-like symptoms.

As this trial is in an early phase, it focuses on understanding safety and determining the optimal dose. Early-phase trials typically provide limited information about long-term safety. However, testing in humans suggests that earlier lab studies indicated it might be safe enough for human trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the cancer vaccine for breast cancer because it represents a novel approach to treatment. Unlike traditional therapies like chemotherapy and hormone therapy, which target rapidly dividing cells or rely on hormone receptors, this vaccine targets specific proteins associated with tumor growth, such as CD105, Yb-1, SOX2, CDH3, and MDM2. This approach harnesses the body's immune system to recognize and attack cancer cells, potentially offering a more targeted and less toxic treatment option. Additionally, the vaccine's delivery as plasmid DNA allows for a streamlined dosing schedule, which could improve patient compliance and outcomes.

What evidence suggests that this trial's vaccine could be effective for breast cancer?

Initial findings suggest that the STEMVAC vaccine, which participants in this trial may receive, could help treat patients with HER2-negative breast cancer. This vaccine targets specific proteins in cancer stem cells that resist chemotherapy and spread the disease. Research has shown that DNA vaccines like this one can train the immune system to fight cancer cells. Early studies demonstrated that DNA vaccines are safe and can trigger a strong immune response. While more data is needed, these early signs offer promise for those battling advanced breast cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02157051

Vaccine Therapy in Treating Patients With HER2-Negative ... This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic acid (DNA) plasmid-based vaccine in treating patients with human ...

2. 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 ...

3. 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 ...

4. trials.outcomes4me.com trials.outcomes4me.com/trial/NCT07078604/2061

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

5. 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 ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-07734

STEMVAC in Patients with Early Stage Triple Negative ... This phase II trial studies the effect of deoxyribonucleic acid (DNA) plasmid- based vaccine (STEMVAC) in patients with curatively treated stage I-III triple ...

7. 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 ...