HER3 Vaccine for Cancer

Overseen By Beth Hollister, BSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Herbert Lyerly

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: CNS metastases, Auto-immune disease, Infection, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a phase I clinical trial will that will use an investigational cancer vaccine called pING-hHER3FL. pING-hHER3FL is a circular piece of DNA that produces the full length human HER3 protein and will be used in a phase I study as immunotherapeutic agent to target cancers that are known to express the human epidermal growth factor receptor HER3. The human epidermal growth factor receptor (HER) family including: HER1 (also known as EGFR), HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important receptor family for the development of many malignancies. HER3 is overexpressed in breast, lung, gastric, head and neck, ovarian cancer, and melanoma. The objectives of this clinical study is to determine the safety and tolerability of pING-hHER3FL in patients with solid tumor malignancies that have been removed surgically and to test whether immunization with pING-hHER3FL can cause a HER3 specific immune response in patients. Patients enrolled in the study will receive pING-hHER3FL by intramuscular injection (IM) every 4 weeks for 3 total doses. Potential benefits of the research include learning the safety of a vaccine targeting HER3 expressing cancers, whether the pING-hHER3FL vaccine can induce HER3 specific immune responses, and see possible clinical benefit to patients receiving pING-hHER3FL.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on continuous steroid therapy or other continuous immunosuppressive drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the HER3 Vaccine for Cancer treatment?

Research shows that vaccines targeting HER3 can activate specific immune cells and antibodies that help slow tumor growth and improve responses to other cancer treatments. This approach has shown promise in delaying tumor growth in breast cancer models and enhancing the effects of immune therapies. ^{1 2 3 4 5}

Is the HER3 vaccine generally safe for humans?

There is no specific safety data available for the HER3 vaccine in humans, but similar vaccines targeting HER1 have been well tolerated in clinical trials, with no severe adverse events reported. ^{1 6 7 8 9}

How is the HER3 Vaccine for Cancer treatment different from other treatments?

The HER3 Vaccine for Cancer, using pING-hHER3FL, is unique because it targets the HER3 receptor, which is often overexpressed in aggressive cancers and resistant to other therapies. This vaccine works by stimulating the immune system to produce specific T cells and antibodies against HER3, potentially enhancing the effectiveness of immune checkpoint inhibitors and slowing tumor growth. ^{1 3 4 10 11}

Eligibility Criteria

Adults who've had surgery for solid tumors like breast, lung, or prostate cancer and finished their standard treatments can join. They should be in good physical shape (ECOG 0 or 1), have a life expectancy over 3 months, and normal organ function. Women must not be pregnant and use birth control. People with autoimmune diseases, active infections, brain metastases, or recent other cancers aren't eligible.

Inclusion Criteria

My recent scans show no signs of cancer.

I've had surgery for cancer, finished chemotherapy, HER2 therapy, and radiation as planned.

I can visit the study site for follow-ups as needed.

Exclusion Criteria

Pregnant or nursing women.

My cancer has spread to my brain.

Medical or psychological impediment to probable compliance with the protocol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pING-hHER3FL by intramuscular injection every 4 weeks for 3 total doses

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Monitoring of relapse-free survival and immune response

5 years

Treatment Details

Interventions

• pING-hHER3FL

Trial Overview The trial is testing pING-hHER3FL—a DNA-based vaccine targeting HER3 protein on cancer cells—given as an injection every four weeks for three doses. It aims to see if it's safe and can trigger the immune system to fight cancer expressing the HER3 protein.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

4 mg pING-hHER3FL ID or IM

Who Is Running the Clinical Trial?

Herbert Lyerly

Lead Sponsor

Trials

5

Recruited

60+

Findings from Research

Immunization with a vaccine targeting HER3 in human HER3 transgenic mouse models of breast cancer successfully induced HER3-specific T cells and antibodies, leading to delayed tumor growth.

Combining the HER3-targeting vaccine with immune checkpoint inhibitors like anti-PD-1 or anti-PD-L1 significantly enhanced T cell infiltration in tumors and improved anti-tumor responses, suggesting a promising strategy for treating HER3-driven malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition. Osada, T., Morse, MA., Hobeika, A., et al.[2021]

Therapeutic vaccines for breast cancer show promise in inducing strong immune responses against tumors, particularly in cases where tumors are weakly immunogenic, with a good safety profile and potential for long-term immune memory.

Clinical trials have demonstrated significant immune responses to vaccines targeting specific tumor antigens like HER2/neu and carcinoembryonic antigen, although achieving clinical efficacy in patients with aggressive metastatic breast cancer remains challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer vaccines: a clinical reality or fairy tale? Curigliano, G., Spitaleri, G., Pietri, E., et al.[2020]

HER-2/neu-specific vaccines have shown the ability to generate long-lasting T-cell immunity against HER-2/neu-positive cancers, such as breast and prostate cancers, with no significant toxicity reported in Phase I and II clinical trials.

Early trials suggest that these vaccines may also help prevent breast cancer relapse in high-risk patients, and future strategies may include multiepitope vaccines and combination therapies to enhance anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER-2/neu as a target for cancer vaccines. Baxevanis, CN., Voutsas, IF., Gritzapis, AD., et al.[2021]

The HER3 cancer vaccine (Ad-HER3) not only stimulates a T cell response but also generates antibodies (HER3-VIAs) that effectively mediate tumor cell destruction through mechanisms like complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).

In mouse models, HER3-VIAs demonstrated significant anti-tumor effects against various breast cancer types, including HER2+ and triple-negative cancers, suggesting that targeting HER3 could be a promising strategy to overcome resistance to existing HER2 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers. Osada, T., Hartman, ZC., Wei, J., et al.[2023]

The study identified novel HER-3 peptide epitopes that can be targeted for active immunotherapy against HER-3 positive cancers, showing promising antitumor responses such as inhibiting cancer cell growth and inducing apoptosis.

Combining HER-3 targeting with other receptor vaccines (like HER-1 and HER-2) enhanced the antitumor effects, suggesting that multi-target immunotherapy could be an effective strategy for treating cancers that overexpress these receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER-3 peptide vaccines/mimics: Combined therapy with IGF-1R, HER-2, and HER-1 peptides induces synergistic antitumor effects against breast and pancreatic cancer cells. Miller, MJ., Foy, KC., Overholser, JP., et al.[2021]

The HER1 vaccine, tested in 12 Macaca fascicularis monkeys over 12 months, induced a strong immune response with high levels of IgG antibodies, indicating its potential effectiveness against epithelial tumors.

The vaccine was well tolerated with a 100% survival rate and minimal local reactions, suggesting it could be safely advanced to clinical trials in human patients with epithelial cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study. Barro, AM., Rivero, AI., Goñi, AL., et al.[2018]

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 HER1-based cancer vaccine was well tolerated in a phase I trial with 24 metastatic castration-resistant prostate cancer patients, showing no severe adverse events and eliciting high levels of anti-HER1 antibodies in most participants.

Patients receiving higher doses of the vaccine demonstrated significant tumor cell recognition and inhibition of HER1 phosphorylation, with a notable trend toward improved survival associated with higher antibody titers and a specific T cell response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Human Epidermal Growth Factor Receptor 1 (HER1)-Based Vaccine in Prostate Castration-Resistant Carcinoma Patients: A Dose-Escalation Phase I Study Trial. Caballero, I., Aira, LE., Lavastida, A., et al.[2020]

Tumor-specific vaccination strategies have been found to be generally safe in early clinical trials involving cancer patients, following promising results in preclinical mouse models.

The effectiveness of these vaccines is likely to be higher in patients with less advanced cancer, and there is a need for better methods to detect both natural and vaccine-induced T cell immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and evaluation of antigen-specific vaccination strategies against cancer. Offringa, R., van der Burg, SH., Ossendorp, F., et al.[2019]

Breast cancer vaccines targeting antigens like HER-2/neu, MUC-1, and hTERT have shown promise in stimulating the immune system to fight cancer, with recent clinical trials indicating potential survival benefits.

These vaccines have been reported to be safe, producing minimal toxicity, which supports their continued development and use in treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the development of a therapeutic vaccine for breast cancer. Coveler, AL., Bates, NE., Disis, ML.[2021]

The study identified nine specific HER3 peptides that can stimulate a strong CD4+ Th1 immune response, which is crucial for attacking tumors, in both healthy individuals and breast cancer patients.

Vaccination with HER3 peptide-pulsed dendritic cells not only prevented tumor development but also significantly delayed tumor growth and caused regression in various HER3-expressing tumor models, highlighting the potential of these peptides in immunotherapy for cancers overexpressing HER3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Immunogenic MHC Class II Human HER3 Peptides that Mediate Anti-HER3 CD4+ Th1 Responses and Potential Use as a Cancer Vaccine. Basu, A., Albert, GK., Awshah, S., et al.[2023]

References

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

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition. [2021]

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

Breast cancer vaccines: a clinical reality or fairy tale? [2020]

3. England pubmed.ncbi.nlm.nih.gov

HER-2/neu as a target for cancer vaccines. [2021]

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

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers. [2023]

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

HER-3 peptide vaccines/mimics: Combined therapy with IGF-1R, HER-2, and HER-1 peptides induces synergistic antitumor effects against breast and pancreatic cancer cells. [2021]

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

Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study. [2018]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Human Epidermal Growth Factor Receptor 1 (HER1)-Based Vaccine in Prostate Castration-Resistant Carcinoma Patients: A Dose-Escalation Phase I Study Trial. [2020]

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

Design and evaluation of antigen-specific vaccination strategies against cancer. [2019]

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

Progress in the development of a therapeutic vaccine for breast cancer. [2021]

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

Identification of Immunogenic MHC Class II Human HER3 Peptides that Mediate Anti-HER3 CD4+ Th1 Responses and Potential Use as a Cancer Vaccine. [2023]