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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed for individuals with certain types of breast cancer resistant to hormone treatment. Researchers aim to determine the vaccine's safety and its effectiveness in boosting the immune system to combat cancer. Participants may qualify if they have estrogen receptor-positive breast cancer and completed standard treatments at least four weeks prior. The trial seeks to improve outcomes for those with resistant forms of breast cancer. 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 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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that peptide vaccines, such as the ESR1 peptide vaccine, can be safely administered to breast cancer patients. Studies have found that these vaccines often trigger immune responses (the body's way of fighting illness) without causing serious side effects. The ESR1 vaccine uses small protein pieces called peptides, along with Montanide ISA and GM-CSF, to enhance the immune system's response.

As this is an early-stage study, the primary goal is to assess the vaccine's safety. Previous patients have tolerated similar treatments well, experiencing only mild reactions like redness or swelling at the injection site. So far, no evidence of major side effects has emerged, suggesting that the vaccine is likely safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which often include surgery, chemotherapy, and hormone therapy, the ESR1 peptide vaccine offers a novel approach by using the body's immune system to target cancer cells. This vaccine is unique because it includes ESR1 peptides combined with Montanide and GM-CSF, which are administered through a series of subcutaneous injections. Researchers are excited about this treatment because it aims to specifically activate the immune system against cancer cells, potentially offering a more targeted and less invasive option compared to traditional therapies.

What evidence suggests that this peptide vaccine might be an effective treatment for breast cancer?

Research has shown that peptide vaccines can safely trigger immune responses in breast cancer patients. This trial tests the ESR1 peptide vaccine as an experimental treatment targeting estrogen receptor-positive breast cancer, a common type. The vaccine uses small protein pieces from the estrogen receptor, combined with GM-CSF and another ingredient to enhance the immune system's response. This combination aims to help the body recognize and attack cancer cells more effectively. Although more studies are needed, early findings suggest potential for improving outcomes in patients whose breast cancer does not respond to hormone therapy. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04270149

Cancer Peptides Plus GM-CSF and Adjuvant in Breast ... A peptide vaccine of these peptides may improve outcomes of patients with endocrine resistant breast cancer.

2. withpower.com withpower.com/trial/phase-1-breast-neoplasms-8-2020-13c00

Peptide Vaccine 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 ...

3. dukecat.com dukecat.com/copy-of-vrp-pembro-study-homepage

Breast Cancer Vaccine Phase II Clinical Trial A Phase I study of cancer peptides plus GM-CSF and adjuvant following completion of prescribed systemic therapy of estrogen receptor positive breast cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8941562/

Development of Peptide-Based Vaccines for Cancer - PMC Unfortunately, a phase III study failed to show efficacy in preventing breast cancer recurrence. Recombinant GM-CSF has been used in peptide vaccine trials ...

5. cancer.gov cancer.gov/clinicaltrials/NCI-2022-01528

A Vaccine (ESR1 Peptide Vaccine) for the Treatment of ... The purpose of this study is to find out if ESR1 peptide vaccine can cause an immune response against ER positive breast cancer and whether it is safe.

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04270149/cancer-peptides-plus-gm-csf-and-adjuvant-in-breast-cancer?activelyRecruiting=false&page=163&id=29&slug=breast-cancer

Cancer Peptides Plus GM-CSF and Adjuvant in Breast ... This is a phase I study looking at the safety of cancer peptides combined with adjuvant and GM-CSF in subjects with estrogen receptor (ESR) ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04270149/

Clinical Trial: NCT04270149 This is a phase I study looking at the safety of cancer peptides combined with adjuvant and GM-CSF in subjects with estrogen receptor (ESR) positive breast ...