H2NVAC Vaccine for Breast Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Amy C. Degnim, M.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mayo Clinic

Must not be taking: Steroids, Antibiotics, others

Disqualifiers: Pregnancy, HIV, Autoimmune disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial studies the H2NVAC vaccine, which aims to boost the immune system to fight breast cancer in patients with HER2-expressing DCIS. The vaccine helps the body recognize and attack cancer cells by targeting the HER2 protein. H2NVAC is a vaccine targeting the HER2 protein, similar to other HER2/neu vaccines being tested for their ability to elicit immune responses against breast cancer.

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.

What data supports the effectiveness of the H2NVAC Vaccine for Breast Cancer?

Research shows that combining HER2-targeted peptide vaccines with other treatments like trastuzumab can enhance immune responses and potentially prevent cancer recurrence. Additionally, multi-epitope vaccines, like H2NVAC, have been shown to induce stronger immune responses in preclinical studies, suggesting they could be effective in treating HER2-positive breast cancer. ^{1 2 3 4 5}

Is the H2NVAC Vaccine for Breast Cancer safe for humans?

Initial safety analysis from a phase II trial of a similar HER2-peptide vaccine showed no significant differences in toxicity, including heart-related issues, compared to standard treatment. This suggests that the vaccine is generally safe for humans. ^{1 2 3 6 7}

How is the H2NVAC vaccine treatment for breast cancer different from other treatments?

The H2NVAC vaccine is unique because it targets multiple specific parts of the HER2 protein, which is often overexpressed in breast cancer, to stimulate a stronger immune response. This multi-epitope approach aims to enhance the body's ability to fight cancer cells more effectively compared to treatments that target a single epitope. ^{1 8 9 10 11}

Research Team

Amy C. Degnim, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Multi-epitope HER2 Peptide Vaccine H2NVAC (Cancer Vaccine)

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.

Participant Groups

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+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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 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]

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]

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(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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

The E75 HER2/neu peptide vaccine. [2022]

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

The clinical development of vaccines for HER2+ breast cancer: Current landscape and future perspectives. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development. [2020]

5. United States 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. [2022]

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

AE37: a novel T-cell-eliciting vaccine for breast cancer. [2014]

7. United States 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. [2020]

8. 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]

9. Netherlands pubmed.ncbi.nlm.nih.gov

HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties. [2014]

10. United States 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. [2021]

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

A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. [2020]