Peptide Vaccine for Breast Cancer

Overseen By Amy Hobeika, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Herbert Lyerly

Must be taking: Endocrine therapies

Must not be taking: Steroids, Immuno-suppressives

Disqualifiers: Autoimmune disease, Cardiac disease, Metastases, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new vaccine made from small pieces of breast cancer proteins, combined with substances that boost the immune system. It targets patients with estrogen receptor positive breast cancer who do not respond well to hormone treatments. The goal is to see if this vaccine is safe and if it can help the immune system fight the cancer more effectively.

Will I have to stop taking my current medications?

The trial allows ongoing endocrine therapies if they have been taken for at least 3 months before joining. However, you cannot be on chemotherapy, radiation, or immunotherapy, and you must stop any steroid therapy at least 6 weeks before starting the trial.

What data supports the effectiveness of the treatment ESR1 peptide vaccine, Cancer Peptides Plus GM-CSF and Adjuvant for breast cancer?

Research shows that peptide vaccines, like the E75 + GM-CSF vaccine, can safely stimulate immune responses in breast cancer patients, suggesting potential effectiveness. Peptide-based vaccines have been shown to trigger specific immune responses against tumor cells, which may help in treating breast cancer. ^{1 2 3 4 5}

Is the peptide vaccine for breast cancer safe for humans?

Research on peptide vaccines, including those combined with GM-CSF, shows they are generally safe in humans, with no severe side effects reported in trials for breast cancer and other conditions. ^{4 5 6 7 8}

How is the ESR1 peptide vaccine treatment different from other breast cancer treatments?

The ESR1 peptide vaccine treatment is unique because it uses specific protein fragments (peptides) to stimulate the immune system to target breast cancer cells, potentially offering a more targeted and less toxic approach compared to traditional therapies. It includes an adjuvant (GM-CSF) to enhance the immune response, which is not a standard component in most breast cancer treatments. ^{2 3 4 5 9}

Eligibility Criteria

This trial is for adults over 18 with a specific type of breast cancer that's been surgically removed but hasn't spread far. They should have finished any standard treatments like chemo at least 4 weeks ago and can't be more than 5 years out from those treatments. Their cancer must be estrogen receptor positive, they need to have certain immune system markers (HLA A0201+), and their organs must function well.

Inclusion Criteria

I have been on hormone therapy for at least 3 months.

My breast cancer was surgically removed, was large or spread to lymph nodes, but not to other parts of my body.

My breast cancer was surgically removed, is ER positive, and I have the HLA A0201+ gene.

Exclusion Criteria

I currently have an infection such as a UTI, HIV, or hepatitis.

Allergies to any component of the vaccine

I have had my spleen removed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 200 mcg ESR1 peptides plus 1ml Montanide and 100 mcg GM-CSF administered subcutaneously over 6 weeks

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

44 days

Long-term follow-up

Detection of ESR mutant-specific memory T cells against at least one of the 5 immunizing peptides by Cytof analysis

2 years

Treatment Details

Interventions

• ESR1 peptide vaccine

Trial Overview The study tests a new vaccine made from cancer peptides targeting the estrogen receptor, combined with GM-CSF and Montanide ISA adjuvant to boost immune response. It aims to check safety first, then how well it triggers an immune reaction in patients who've resisted hormone therapy.

Participant Groups

Group I: ESR1 peptide vaccine Experimental Treatment 1 Intervention

200 mcg ESR1 peptides plus 1ml Montanide and 100 mcg GM-CSF administered subcutaneously weeks 0, 1, 2, 4, 5, 6 for a total of 6 injections.

Who Is Running the Clinical Trial?

Herbert Lyerly

Lead Sponsor

Trials

5

Recruited

60+

Findings from Research

The study involved 22 patients with metastatic (15) and stage II-III (7) breast cancer who received an autologous GM-CSF-secreting vaccine, showing that the vaccine can induce immune responses with limited side effects.

Among patients with metastatic disease, one patient remained disease-free for 13 years, while others experienced stable disease for several months, indicating potential long-term benefits of the vaccine despite some patients progressing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers. Anderson, KS., Erick, TK., Chen, M., et al.[2023]

Peptide-based vaccines targeting tumor-associated antigens (TAAs) like MUC1, HER2/neu, and CEA have shown promise in eliciting specific immune responses in breast cancer, as demonstrated in various clinical trials including phases I to III.

These vaccines are advantageous because they offer a more specific and less toxic treatment option compared to traditional therapies, with studies like NeuVax and DPX-0907 highlighting their efficacy as neoadjuvant immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide vaccines in breast cancer: The immunological basis for clinical response. Peres, Lde P., da Luz, FA., Pultz, Bdos A., et al.[2022]

In a study of 186 breast cancer patients, those vaccinated with the E75 + GM-CSF vaccine showed a lower recurrence rate (8.3%) compared to the control group (14.8%), although this difference was not statistically significant (P = 0.17).

Vaccinated patients who did experience recurrences had more aggressive disease characteristics, such as higher tumor grades and nodal stages, but they exhibited similar immune responses to the vaccine as those who did not recur, suggesting that the vaccine may still provide some protective benefits against more aggressive forms of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Amin, A., Benavides, LC., Holmes, JP., et al.[2020]

The HER-2/neu E75-peptide vaccine, combined with GM-CSF, is safe and effectively stimulates E75-specific CD8(+) T cell immunity in breast cancer patients, with a booster enhancing this response.

Immunity from the initial vaccination wanes over time, but a booster given around 6 months after the primary series significantly increases E75-specific immunity, especially in patients who initially lacked elevated residual immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Holmes, JP., Clifton, GT., Patil, R., et al.[2014]

Peptide-based vaccines targeting tumor-associated antigens (TAAs) in breast cancer have been under development for over 20 years, showing promise in eliciting specific immune responses without serious side effects in clinical trials.

Research has focused on enhancing vaccine efficacy by identifying more immunogenic peptides and optimizing combinations with adjuvants, which could lead to stronger immune responses and improved T-cell memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide-based vaccination and induction of CD8+ T-cell responses against tumor antigens in breast cancer. Harao, M., Mittendorf, EA., Radvanyi, LG.[2020]

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]

The combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) was found to be safe for patients with castration-resistant prostate cancer (CRPC), with no serious treatment-related adverse events reported and only mild skin reactions observed.

The treatment successfully boosted immune responses in a significant portion of patients, with 67% showing enhanced cytotoxic T lymphocyte responses, and a median survival time of 23.8 months, suggesting promising antitumor activity that warrants further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. Noguchi, M., Uemura, H., Naito, S., et al.[2013]

In a study of 10 patients with advanced melanoma, individualized peptide vaccinations combined with GM-CSF showed promising results, with a median progression-free survival of 6 months after a mean of 6.5 vaccination cycles.

The treatment was well tolerated, with most patients experiencing only mild side effects, and 5 out of 10 patients remained relapse-free for over a year, indicating potential efficacy and safety for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients. Atzpodien, J., Fluck, M., Reitz, M.[2012]

In a study involving 99 breast cancer patients, the optimal biologic dose (OBD) of the E75 vaccine combined with GM-CSF was found to be 1000 microg E75 plus 250 microg GM-CSF, administered monthly for 6 months, showing similar toxicity levels compared to lower doses.

Patients receiving the optimal dose exhibited a significantly larger immune response, indicated by a greater delayed type hypersensitivity (DTH) reaction and a trend towards reduced cancer recurrence, suggesting that the E75 vaccine may enhance immunity against HER-2/neu in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Holmes, JP., Gates, JD., Benavides, LC., et al.[2008]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Peptide vaccines in breast cancer: The immunological basis for clinical response. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. [2020]

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

Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. [2014]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Peptide-based vaccination and induction of CD8+ T-cell responses against tumor antigens in breast cancer. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer. [2021]

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

A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. [2013]

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

Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients. [2012]

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

Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. [2008]