Mammaglobin-A DNA Vaccine for Breast Cancer

Not currently recruiting at 2 trial locations

Overseen By William E Gillanders, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Endocrine therapy, Chemotherapy

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Metastatic disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new DNA vaccine for breast cancer to determine its safety and ability to help the immune system fight cancer cells. The vaccine targets a protein called mammaglobin-A, found in high amounts on breast cancer cells. Participants will receive standard cancer therapies, with some also receiving the Mammaglobin-A DNA Vaccine to assess its impact on their immune response. The trial seeks individuals newly diagnosed with certain types of breast cancer that have not spread and who plan to undergo surgery. 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. However, you cannot participate if you are on certain treatments like surgery, radiation, or investigational agents for your cancer, except for specific therapies mentioned in the trial.

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

Research shows that the mammaglobin-A DNA vaccine is safe for people. Earlier studies with patients who have advanced breast cancer found that the vaccine was well-tolerated. Participants did not experience major side effects, and the treatment successfully activated the immune system to fight cancer cells. This indicates the vaccine can be used without causing serious problems. Although this trial is still in the early stages, safety data from past research provides a strong basis for its use in patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Mammaglobin-A DNA vaccine for breast cancer because it introduces a novel approach by using a DNA-based vaccine to target mammaglobin-A, a protein often overexpressed in breast cancer cells. Unlike traditional therapies such as chemotherapy and endocrine therapy, which broadly attack cancer cells, this vaccine aims to stimulate the immune system to specifically recognize and destroy cancer cells with mammaglobin-A. Additionally, the vaccine is administered via a TriGrid electroporation device, which enhances the uptake of DNA into cells, potentially increasing the vaccine's effectiveness. This targeted and innovative mechanism of action offers a new avenue for treating breast cancer, sparking interest and hope among researchers.

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

Research has shown that the Mammaglobin-A DNA vaccine holds promise for treating breast cancer. In this trial, some participants will receive the Mammaglobin-A DNA vaccine alongside standard therapies. Studies have found that this vaccine is safe and can activate the immune system to specifically target breast cancer cells. Early results suggest that patients who received the Mammaglobin-A DNA vaccine experienced longer periods without their cancer worsening. The vaccine trains the immune system to recognize and attack mammaglobin-A, a protein often found in large amounts on breast cancer cells. This method aims to help the body fight cancer more effectively. ^{1 2 3 6 7}

Who Is on the Research Team?

William E Gillanders, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for postmenopausal or premenopausal breast cancer patients aged 18+, with ER+ and HER2- tumors aiming for surgery. They must have a measurable lesion expressing mammaglobin-A, be responding to neoadjuvant therapy, and have good organ function. Exclusions include pregnancy, known metastasis, recent investigational drugs use, vaccine allergies, uncontrolled illnesses, HIV-positive status, high non-adherence risk or obscured injection sites.

Inclusion Criteria

My breast cancer is ER+ and HER2-, aiming for surgery to remove the tumor and affected lymph nodes.

My organs and bone marrow are working well.

My doctor thinks my treatment before surgery is working, or my tumor growth rate is low.

Exclusion Criteria

My cancer has spread to other parts of my body.

Individuals in whom the ability to observe possible local reactions at the eligible injection sites is unacceptably obscured due to a physical condition or permanent body art

I have had a biopsy of lymph nodes in my armpit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant endocrine therapy or chemotherapy, with mammaglobin-A DNA vaccine administered at Days 28, 56, and 84

12 weeks

3 visits for vaccine administration

Follow-up

Participants are monitored for safety and immune response, with assessments including ELISPOT analyses and cytokine expression analyses

52 weeks

Multiple visits for blood sampling and assessments

Long-term follow-up

Participants are monitored for progression-free survival and objective tumor response rate

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Mammaglobin-A DNA Vaccine

Trial Overview The study tests the safety and immune response of a Mammaglobin-A DNA Vaccine in breast cancer patients undergoing endocrine therapy before surgery. The vaccine contains mammaglobin-A gene DNA which may help the immune system fight cancer cells by recognizing them more effectively.

How Is the Trial Designed?

Group I: Cohort 4: Neoadjuvant chemotherapy + mammoglobin-A DNA vaccine Experimental Treatment 2 Interventions

* Will be treated with standard of care neoadjuvant chemotherapy as determined by their treating physician * If archival tissue not sufficient, a research biopsy to obtain primary tissue must be done prior to day 28 * Treated with 4 mg of mammaglobin-A DNA vaccine at 3 time points (Days 28, 56, and 84) * All study injections will be administered using a TriGrid electroporation device * Subjects who begin neoadjuvant endocrine therapy but are determined to not be responding at the Day 14 biopsy may begin chemotherapy treatment, at the discretion of the treating physician. These subjects may be enrolled in either cohort 4

Group II: Cohort 2:Neoadjuvant endocrine + mammaglobin-A DNA vaccine Experimental Treatment 2 Interventions

* Will be treated with standard of care adjuvant endocrine therapy * Optional biopsy approximately 14 days following initiation of neoadjuvant therapy * Treated with 4 mg of mammaglobin-A DNA vaccine at 3 time points (Days 28, 56, and 84) * All study injections will be administered using a TriGrid electroporation device

Group III: Cohort 1:Neoadjuvant endocrine therapy alone Active Control 1 Intervention

* Will be treated with standard of care adjuvant endocrine therapy as determined by their treating physician * Optional biopsy approximately 14 days following initiation of neoadjuvant therapy

Group IV: Cohort 3: Neoadjuvant chemotherapy alone Active Control 1 Intervention

* Will be treated with standard of care neoadjuvant chemotherapy as determined by their treating physician * If archival tissue not sufficient, a research biopsy to obtain primary tissue must be done prior to day 28 * Subjects who begin neoadjuvant endocrine therapy but are determined to not be responding at the Day 14 biopsy may begin chemotherapy treatment, at the discretion of the treating physician. These subjects may be enrolled in cohort 3

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Published Research Related to This Trial

A phase 1 clinical trial has shown that the mammaglobin-A DNA vaccine is safe for patients with metastatic breast cancer, indicating its potential for further development.

Currently, a phase 1b trial is enrolling early-stage breast cancer patients to assess the vaccine's effects when given alongside neoadjuvant endocrine therapy, allowing researchers to study its impact on the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mammaglobin-A is a target for breast cancer vaccination. Kim, SW., Goedegebuure, P., Gillanders, WE.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4801441/

Mammaglobin-A is a target for breast cancer vaccination We recently completed a phase 1 clinical trial demonstrating the safety of a mammaglobin-A DNA vaccine in patients with metastatic breast cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00807781

Mammaglobin-A DNA Vaccine for Metastatic Breast Cancer The purpose of this study is to evaluate the safety of mammaglobin-A DNA vaccine in metastatic breast cancer patients. Detailed Description.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4322416/

Safety and preliminary evidence of biological efficacy of a ... The MAM-A DNA vaccine is safe, capable of eliciting MAM-A-specific CD8 T cell responses, and preliminary evidence suggests improved progression-free survival.

4. tandfonline.com tandfonline.com/doi/full/10.2217/imt.15.40

Full article: Developing a Clinical Development Paradigm ... Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer. Clin.

5. aacrjournals.org aacrjournals.org/clincancerres/article-abstract/20/23/5964/13865

Safety and Preliminary Evidence of Biologic Efficacy of a ... Data from Safety and Preliminary Evidence of Biologic Efficacy of a Mammaglobin-A DNA Vaccine in Patients with Stable Metastatic Breast Cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02204098

Safety and Immune Response to a Mammaglobin-A DNA ... The purpose of this research study is to find out about the safety of injecting the gene (DNA) for mammaglobin-A into people with breast cancer.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02204098/

Clinical Trial: NCT02204098 The purpose of this research study is to find out about the safety of injecting the gene (DNA) for mammaglobin-A into people with breast ...