H2NVAC Vaccine for Breast Cancer

Recruiting at 1 trial location

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Steroids, Antibiotics, others

Disqualifiers: Pregnancy, HIV, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 7

Duration: 8 weeks

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new vaccine, H2NVAC, to determine the optimal dose and observe side effects in treating ductal carcinoma in situ, a type of breast cancer. The vaccine is designed to enhance the body's immune response and potentially combat cancer cells. The trial seeks participants diagnosed with ductal carcinoma in situ who have not received prior treatment for this condition and show HER2 protein presence in their cancer. Participants will receive the vaccine before surgery to assess its interaction with the immune system. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Do I need to stop taking my current medications for the trial?

The trial requires that you stop any endocrine therapy (like tamoxifen or aromatase inhibitors) at least 2 months before starting the study. You cannot use these therapies during the vaccination period, but you can resume them after the vaccination and surgery.

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

Research has shown that the H2NVAC vaccine was well-tolerated in earlier studies. In one study, participants did not experience any serious side effects that required stopping the treatment. Only mild side effects, rated as grades 1 and 2, were observed. This suggests that the vaccine is generally safe for people. However, it's important to remember that this is still an early study phase, which mainly focuses on assessing the treatment's safety and determining the best dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which often involve surgery, chemotherapy, and targeted therapies like trastuzumab, the H2NVAC vaccine introduces a novel approach by using a multi-epitope HER2 peptide. This vaccine is designed to train the immune system to recognize and attack HER2-positive cancer cells, potentially leading to a more precise immune response with fewer side effects. Additionally, the inclusion of GM-CSF enhances the immune system's response to the vaccine, offering a promising strategy to prevent cancer recurrence. Researchers are excited about this treatment because it represents a shift towards harnessing the body's own defenses to fight cancer, which could lead to more personalized and effective care.

What evidence suggests that the H2NVAC vaccine might be an effective treatment for breast cancer?

Research shows that the H2NVAC vaccine, which participants in this trial will receive, is designed to help the immune system fight breast cancer, particularly HER2-expressing ductal carcinoma in situ. Earlier studies found that this vaccine is safe and enhances the immune system's T and B cells to respond strongly and for an extended period. This suggests the vaccine might improve the body's ability to fight cancer cells. Although the full effects are still under investigation, early results are promising and demonstrate a strong immune response. Therefore, the vaccine could offer a new method to prevent or slow the progression of breast cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Amy C. Degnim, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with operable ductal carcinoma in situ of the breast expressing any level of HER2, who haven't had prior treatment for it. They must have good blood counts and organ function, not be pregnant or breastfeeding, agree to use contraception, and can't be on certain other treatments. People with severe diseases or conditions that could interfere with the study are excluded.

Inclusion Criteria

Your white blood cell count is normal.

Willing to provide blood samples for correlative research purposes

I have not had any treatment for my current DCIS.

Exclusion Criteria

Pregnant women

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

You have a known autoimmune disease, like type I diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GM-CSF admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally. Treatment repeats every 14 days for up to 4 cycles for dose levels 1 and 2, and on days 1, 4, 8, and 15 for 1 cycle for dose level 3.

8 weeks

4 visits (in-person) for dose levels 1 and 2, 4 visits (in-person) for dose level 3

Surgery

Standard of care surgery is performed after completion of the vaccine treatment cycles.

Follow-up

Participants are monitored for safety and effectiveness after surgery at 3, 6, and 12 months, with optional follow-up at 18 and 24 months.

24 months

3 visits (in-person) with optional additional visits

What Are the Treatments Tested in This Trial?

Interventions

• Multi-epitope HER2 Peptide Vaccine H2NVAC

Trial Overview The trial is testing a new vaccine called H2NVAC given before surgery to stimulate immune cells against breast cancer in those with HER2-expressing ductal carcinoma in situ. It aims to find the best dose and observe side effects while also collecting biospecimens and conducting heart checks.

How Is the Trial Designed?

Group I: Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF) Experimental Treatment 6 Interventions

Prior to standard of care surgery, patients treated at dose levels 1 and 2 receive GM-CSF admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on day 1 of each cycle. Treatment repeats every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients treated at dose level 3 receive GM-CSF admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on days 1, 4, 8, and 15 for 1 cycle. Patients also undergo ECHO and collection of blood samples throughout the trial and may undergo biopsy on trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The MFCH401-based tricomponent anti-HER2 cancer vaccine significantly enhances the immune response against HER2-overexpressing breast cancer cells, showing stronger humoral and cellular immunity compared to simpler two-component vaccines.

Incorporating the lipopeptide Pam3CSK4 into the vaccine formulation was found to provide superior immunostimulatory activity, improving the overall effectiveness of the vaccine in targeting breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines. Feng, Q., Yu, X., Wang, Y., et al.[2022]

A multiepitope vaccine targeting the HER-2 oncoprotein was developed using computer-aided analysis, which showed promising results in inducing high levels of antibodies that inhibited tumor growth in rabbits.

Combining two specific chimeric vaccines enhanced immune responses, leading to a significant reduction in pulmonary metastases in a cancer model, suggesting potential for treating HER-2-associated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. Dakappagari, NK., Pyles, J., Parihar, R., et al.[2020]

HER2 is a key target in breast cancer treatment, as it is over-expressed in 20-30% of cases, and therapies using HER2-directed monoclonal antibodies have significantly improved outcomes for patients with these tumors.

While early phase clinical trials have shown promise for HER2 vaccines, late phase trials have not yet produced clinically relevant results, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical development of vaccines for HER2+ breast cancer: Current landscape and future perspectives. Costa, RLB., Soliman, H., Czerniecki, BJ.[2017]

A phase II trial involving 150 patients with HER2 low-expressing breast cancer showed that combining the HER2-peptide vaccine nelipepimut-S with trastuzumab did not increase toxicity compared to trastuzumab alone, indicating a favorable safety profile.

The study aims to assess the clinical efficacy of this combination therapy, with results expected 6 months after the final patient enrollment, potentially offering new treatment options for patients who currently do not benefit from HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial safety analysis of a randomized phase II trial of nelipepimut-S + GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors. Clifton, GT., Peace, KM., Holmes, JP., et al.[2020]

Passive immunotherapy using monoclonal antibodies like trastuzumab and pertuzumab has significantly improved treatment outcomes for HER2-positive breast cancer, but challenges such as resistance and disease relapse remain.

There is a growing interest in active immunotherapy using HER2-derived peptide vaccines, along with other immunotherapeutic strategies like CTLA-4 inhibitors and PD-1/PD-L1 antibodies, to enhance immune responses against HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development. Arab, A., Yazdian-Robati, R., Behravan, J.[2020]

The combination of the HER2-targeted peptide vaccine nelipepimut-S (NPS) with trastuzumab was found to be safe, showing no additional toxicity compared to the control group in a study of 275 patients with HER2 low-expressing breast cancer.

While the overall disease-free survival (DFS) did not significantly differ between the NPS and control groups, patients with triple-negative breast cancer (TNBC) showed a significant improvement in DFS with NPS, indicating potential for further research in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Randomized Phase IIb Trial of Nelipepimut-S + Trastuzumab versus Trastuzumab to Prevent Recurrences in Patients with High-Risk HER2 Low-Expressing Breast Cancer. Clifton, GT., Hale, D., Vreeland, TJ., et al.[2022]

The E75 vaccine, tested in two Phase II trials with 186 breast cancer patients, shows promise in preventing disease recurrence, particularly in high-risk individuals with node-positive and node-negative disease.

The trials highlighted the importance of optimal dosing and booster inoculations for enhancing the vaccine's effectiveness, while also providing insights into the immunologic responses and potential clinical benefits of this targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The E75 HER2/neu peptide vaccine. Mittendorf, EA., Holmes, JP., Ponniah, S., et al.[2022]

The HER-2(9(657)) peptide, derived from the HER-2/neu oncoprotein, has been identified as a strong candidate for a cancer vaccine, showing high affinity for HLA-A2.1 and inducing a robust immune response in HLA-A2.1 transgenic mice.

In preclinical studies, this peptide not only triggered specific cytotoxic T lymphocyte (CTL) responses but also enabled mice to reject established tumors and develop long-lasting immunity, indicating its potential effectiveness in treating HER-2/neu positive breast cancer in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties. Gritzapis, AD., Fridman, A., Perez, SA., et al.[2014]

The AE37 vaccine, which targets the HER-2/neu protein in breast cancer, has been shown to be safe and effective in generating long-lasting immune responses in patients, regardless of their HER-2/neu expression levels.

Early clinical trials indicate that the AE37 vaccine may help prevent breast cancer recurrence, highlighting its potential as a promising immunotherapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AE37: a novel T-cell-eliciting vaccine for breast cancer. Sears, AK., Perez, SA., Clifton, GT., et al.[2014]

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 study identified 84 HLA-DR epitopes of the HER-2/neu antigen, with four specific epitopes (p59, p88, p422, and p885) showing high binding affinity and preexisting T-cell immunity in over 58% of breast and ovarian cancer patients.

The findings suggest that these epitopes could enhance the effectiveness of HER-2/neu-targeting vaccines, as they are naturally processed by antigen-presenting cells and are applicable to approximately 84% of the population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A degenerate HLA-DR epitope pool of HER-2/neu reveals a novel in vivo immunodominant epitope, HER-2/neu88-102. Karyampudi, L., Formicola, C., Erskine, CL., et al.[2021]

Citations

1. mayo.edu mayo.edu/research/clinical-trials/cls-20439962

A Vaccine (H2NVAC) Before Surgery for the Treatment of ... This phase Ib trial studies the side effects and best dose of a vaccine called H2NVAC before surgery in treating patients with HER2 expressing ductal carcinoma ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7828795/

Cancer Vaccines, Treatment of the Future: With Emphasis ... Results concluded that the 5-year disease-free survival (DFS) was 89.7% for those who received E75 and 80.2% in those who received placebo, ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/239219

Neoadjuvant Multi-epitope HER2 Peptide Vaccine in ... This interventional clinical study will examine the safety and efficacy of a degenerate subdominant HER2 specific helper T cell epitope vaccine (H2NVAC) in ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.550

Safety run-in phase of the multi-epitope HER2 peptide ... Our previous phase I trial showed that this vaccine was safe and generated robust, long-lasting T and B cell immune responses. Methods: Patients ...

5. withpower.com withpower.com/trial/phase-1-carcinoma-3-2019-fc947

H2NVAC Vaccine for Breast Cancer This trial studies the H2NVAC vaccine, which aims to boost the immune system to fight breast cancer in patients with HER2-expressing DCIS.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04144023

A Vaccine (H2NVAC) Before Surgery for the Treatment of ... To determine the safety and tolerability of multi-epitope HER2 peptide vaccine H2NVAC (H2NVAC) given for 4 treatments in patients with HER2-expressing ductal ...

7. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/her2-positive-breast-cancer

HER2-Positive Breast Cancer Clinical Trials This phase Ib trial studies the side effects and best dose of a vaccine called H2NVAC before surgery in treating patients with HER2 expressing ductal carcinoma ...