Vaccine Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Xin Bryan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pravin T.P Kaumaya

Must not be taking: Targeted therapies

Disqualifiers: Active infection, HIV, Hepatitis, Autoimmune, others

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

Compensation: Varies

Number of Visits: 21

Duration: up to 92 days

42 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, patients on certain targeted therapies or those requiring corticosteroids or other immunosuppressives are not eligible, which might imply some restrictions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment for breast cancer?

Research suggests that combining HER2-targeted therapies with cancer vaccines can enhance the immune response against breast cancer. Specifically, combining trastuzumab (a HER2-targeted therapy) with HER2-targeted cancer vaccines has shown benefits in certain types of breast cancer, indicating potential effectiveness of similar vaccine therapies. ^{1 2 3 4 5}

Is the MVF-HER-2 vaccine therapy for breast cancer safe for humans?

The MVF-HER-2 vaccine therapy, similar to other HER2-based treatments, has been generally well tolerated in clinical trials, with most side effects being mild (grade 1/2 adverse events). No serious heart-related issues were reported, and the treatment was associated with minimal toxicity. ^{3 5 6 7 8}

How does the MVF-HER-2 vaccine treatment for breast cancer differ from other treatments?

The MVF-HER-2 vaccine treatment is unique because it combines specific HER-2 protein segments with an adjuvant (a substance that enhances the body's immune response) to stimulate both B and T cell responses, potentially offering a more targeted and effective immune attack against breast cancer cells compared to other vaccines that may focus on a single type of immune response. ^{5 9 10 11 12}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of vaccine therapy in treating patients with metastatic solid tumors. Vaccines made from antibodies and peptides combined with tumor cells may help the body build an effective immune response to kill tumor cells.

Research Team

Pravin Kaumaya, PhD

Principal Investigator

Indiana University

Eligibility Criteria

This trial is for patients with metastatic solid tumors, specifically those with breast cancer or gastrointestinal cancers that show an overexpression of a protein called Epidermal Growth Factor Receptor (EGFR).

Inclusion Criteria

I have breast or gastrointestinal cancer that cannot be removed by surgery.

I had brain metastases treated, off steroids, and stable for 3+ months.

Women of child-bearing potential must not be pregnant and must have a negative pregnancy test. Men and women must agree to practice effective contraception while on this study

Exclusion Criteria

I am allergic to specific components used in the trial.

I have been off antibiotics for 3 weeks and am clear of infection.

Patients who have developed anaphylactic responses to other vaccines

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the HER-2 B Cell Peptide Vaccine to study side effects and best dose

up to 92 days

Multiple visits for vaccine administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 1 year

Follow-up visits at 21 days, 6 months, and 1 year post initial vaccination

Treatment Details

Interventions

• Combination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with ISA 720

Trial Overview The study is testing vaccine therapy combining two peptides, MVF-HER-2 (597-626) and MVF-HER-2 (266-296), mixed with ISA 720 to see if it can stimulate the immune system to destroy tumor cells.

Participant Groups

Group I: HER-2 vaccine GI Experimental Treatment 1 Intervention

Group II: HER-2 vaccine Breast Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Pravin T.P Kaumaya

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

In a study involving female BALB/c mice, the combination of the MUC1 gene vaccine and GM-CSF adjuvant significantly inhibited the growth of EMT6 breast cancer tumors, with tumor sizes reduced to 135 mm³ compared to 596 mm³ in the control group.

The presence of GM-CSF not only enhanced the overall antitumor effect of the MUC1 vaccine but also increased the cytotoxicity of MUC1-specific T cells, demonstrating a more effective immune response against the cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Enhanced inhibitory effect of MUC1 gene vaccine on breast cancer growth by GM-CSF]. Yuan, SF., Li, KZ., Wang, L., et al.[2019]

HER2-targeted therapies, like trastuzumab, have shown promising immunomodulatory effects that can enhance the treatment of HER2-overexpressing cancers, but more options are still needed.

Preclinical studies indicate that combining HER2-targeted therapies with immunotherapies, such as checkpoint inhibitors and cancer vaccines, may provide synergistic benefits, particularly in specific patient populations like those with PD-L1+ breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy as a partner for HER2-directed therapies. Clifton, GT., Peoples, AGE.[2022]

In a phase III trial involving 758 women with HER2 low-expressing breast cancer, the combination of nelipepimut-S (NP-S) and GM-CSF was well tolerated, with common side effects being mild injection site reactions.

The interim analysis showed no significant difference in disease-free survival (DFS) between the NP-S group and the placebo group, although NP-S did lead to a higher detection rate of recurrence events through imaging in asymptomatic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial. Mittendorf, EA., Lu, B., Melisko, M., et al.[2020]

Recent trials show that new HER2-targeted agents like pertuzumab and trastuzumab emtansine (T-DM1) are effective in treating HER2-positive breast cancer, with T-DM1 being a powerful combination of trastuzumab and a cytotoxic agent.

Combining trastuzumab with lapatinib or pertuzumab has led to significantly better outcomes, nearly doubling the rates of complete response in patients, indicating a shift towards dual anti-HER2 therapies to overcome resistance in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging strategies for the dual inhibition of HER2-positive breast cancer. Konecny, GE.[2019]

The E75 vaccine demonstrated significant effectiveness in improving immune responses and clinical outcomes, such as reduced recurrence rates and increased disease-free survival in breast cancer patients, with minimal side effects reported.

The GP2 vaccine also showed promise in eliciting immune responses, particularly in increasing CD8+ T-cell numbers, but further clinical trials are necessary to establish its efficacy compared to the E75 vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis. You, Z., Zhou, W., Weng, J., et al.[2021]

The dHER2 immunotherapeutic combined with the AS15 immunostimulant was well tolerated in 40 patients with HER2-positive metastatic breast cancer, showing minimal toxicity and no cardiac events, which is important for patient safety.

Clinical activity was demonstrated with one complete response lasting 11 months and one partial response lasting 3.5 months, along with stable disease in 10 patients for at least 26 weeks, indicating potential efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer. Curigliano, G., Romieu, G., Campone, M., et al.[2021]

In a study of 39 elderly patients with HER-2-positive breast cancer, 82.1% completed one year of trastuzumab treatment, indicating good tolerance to the therapy.

While 28.2% experienced adverse events, including congestive heart failure and lower left ventricular ejection fraction, most patients managed to recover with appropriate treatment, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of adjuvant trastuzumab for HER-2-overexpressing elderly breast cancer patients: a multicenter cohort study. Sawaki, M., Mukai, H., Tokudome, N., et al.[2015]

The combination of the HER2-based vaccine dHER2 and lapatinib was found to be safe for patients with HER2-overexpressing metastatic breast cancer, showing no cardiotoxicity and inducing anti-HER2-specific antibodies in all participants (n=12).

Despite a median time to progression of 55 days, the treatment demonstrated promising long-term survival, with a 300-day overall survival rate of 92%, indicating potential effectiveness in patients who are refractory to trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. Hamilton, E., Blackwell, K., Hobeika, AC., et al.[2023]

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]

E75, an immunogenic peptide from the HER2 protein, has been shown to be safe and effective in stimulating an immune response in breast cancer patients when used as a vaccine with an immunoadjuvant.

In a study of 187 patients, those vaccinated with E75 + GM-CSF had a 5-year disease-free survival rate of 89.7%, significantly higher than the 80.2% in the control group, indicating a 48% reduction in the risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of the E75 Vaccine in Breast Cancer. Clifton, GT., Gall, V., Peoples, GE., et al.[2020]

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]

The GP2 vaccine, when administered with GM-CSF, was found to be safe with minimal toxicities in a phase II trial involving 180 breast cancer patients, indicating its potential for use in clinical settings.

Although the overall analysis did not show a significant benefit in disease-free survival compared to the control group, there were promising results in patients with HER2 overexpression, suggesting that the vaccine may be more effective in this subgroup when the full treatment series is completed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. Mittendorf, EA., Ardavanis, A., Litton, JK., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Enhanced inhibitory effect of MUC1 gene vaccine on breast cancer growth by GM-CSF]. [2019]

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

Immunotherapy as a partner for HER2-directed therapies. [2022]

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

Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Emerging strategies for the dual inhibition of HER2-positive breast cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis. [2021]

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

A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Safety of adjuvant trastuzumab for HER-2-overexpressing elderly breast cancer patients: a multicenter cohort study. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Development of the E75 Vaccine in Breast Cancer. [2020]

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]

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

Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. [2022]