Mammaglobin-A DNA Vaccine for Breast Cancer

Recruiting at 1 trial location

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

27 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. 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.

What data supports the effectiveness of the Mammaglobin-A DNA Vaccine treatment for breast cancer?

Research shows that the Mammaglobin-A DNA Vaccine is safe and can increase the number of immune cells that target breast cancer cells, suggesting it might help the body fight the cancer. ^{1 2 3 4 5}

Is the Mammaglobin-A DNA Vaccine safe for humans?

The Mammaglobin-A DNA Vaccine has been shown to be safe in a phase 1 clinical trial involving patients with metastatic breast cancer. ^{1 2 4 6 7}

How is the Mammaglobin-A DNA vaccine treatment different from other breast cancer treatments?

The Mammaglobin-A DNA vaccine is unique because it targets a protein overexpressed in most breast cancers, aiming to stimulate the body's immune system to attack cancer cells specifically. Unlike traditional treatments, this vaccine works by enhancing the body's natural immune response, particularly activating CD8+ T cells, to recognize and destroy cancer cells. ^{1 2 3 4 5}

What is the purpose of this trial?

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. The DNA used in this study was purified from bacteria and contains the gene for mammaglobin-A. Mammaglobin-A is a protein that is highly expressed by breast cancer cells. Injection of mammaglobin-A DNA may be a way to generate an immune response to breast cancer cells. There is evidence that an immune response may be a way to fight cancer. In addition to evaluating the safety of the mammaglobin-A injection, this study is also looking at the immune response that the participant's body has after each injection.

Research Team

William E Gillanders, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer. [2020]

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

Mammaglobin-A is a target for breast cancer vaccination. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of the role of CD8+T cells in breast cancer immunity following mammaglobin-A DNA vaccination using HLA-class-I tetramers. [2011]

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

Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Oligodeoxynucleotides ODN 2006 and M362 Exert Potent Adjuvant Effect through TLR-9/-6 Synergy to Exaggerate Mammaglobin-A Peptide Specific Cytotoxic CD8+T Lymphocyte Responses against Breast Cancer Cells. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Prevention of metastases with a Mage-b DNA vaccine in a mouse breast tumor model: potential for breast cancer therapy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Insertion of the DNA for the 163-171 peptide of IL1beta enables a DNA vaccine encoding p185(neu) to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice. [2020]