HER2 DC1 Vaccine + Chemotherapy for Breast Cancer

Overseen By Jennifer Childress

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Paclitaxel, Trastuzumab, Pertuzumab

Must not be taking: Immunosuppressants

Disqualifiers: Inflammatory breast cancer, Uncontrolled illness, 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)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a new vaccine, the Dendritic Cell (DC1) vaccine, to standard chemotherapy can improve treatment for individuals with HER2-positive breast cancer. Participants will receive standard chemotherapy drugs such as Paclitaxel, Pertuzumab, and Trastuzumab, along with the DC1 vaccine. This study targets those with specific types of HER2-positive breast cancer suitable for pre-surgery treatment. Individuals diagnosed with HER2-positive breast cancer requiring chemotherapy before surgery might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on other investigational agents for breast cancer treatment or require systemic immunosuppressant drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the HER2 DC1 vaccine, tested in this trial, was safe in earlier studies. Most patients experienced only mild side effects, such as soreness at the injection site or mild flu-like symptoms.

The other treatments in the trial—Paclitaxel, Pertuzumab, and Trastuzumab—are already approved for breast cancer treatment, and their safety is well-established. Common side effects of these drugs include tiredness, hair loss, and nausea, while serious side effects remain rare.

Overall, earlier research and existing approvals indicate that the treatments in this trial are generally safe. However, like any medical treatment, some risks exist. Discuss these risks with the trial team before deciding to participate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the HER2 DC1 Vaccine combined with chemotherapy for breast cancer because it introduces a novel approach that targets the immune system directly. Unlike standard treatments like chemotherapy alone, this vaccine is designed to stimulate the body's dendritic cells, enhancing their ability to recognize and attack cancer cells. The potential for this vaccine to work synergistically with existing drugs like Paclitaxel, Pertuzumab, and Trastuzumab offers a promising boost in treatment effectiveness. This unique mechanism of engaging the immune system could lead to improved outcomes for patients, especially those with challenging HER2-positive breast cancer.

What evidence suggests that this trial's treatments could be effective for HER2 positive breast cancer?

Research has shown that the HER2 DC1 vaccine can help the immune system fight HER2-positive breast cancer. In this trial, participants will receive different doses of the DC1 vaccine to evaluate its safety and effectiveness. Studies have found that this vaccine encourages T-cells, a type of immune cell, to find and attack cancer cells. This method has shown promise in improving immune responses in early breast cancer cases. The DC1 vaccine trains the body to better recognize and combat HER2 cancer cells. Early results suggest it could be a valuable addition to treatments like chemotherapy for improved outcomes. ^{3 5 6 7 8}

Who Is on the Research Team?

Hyo (Heather) Han, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage I-III HER2+ breast cancer, measurable by exam or imaging. They must be fit for neoadjuvant chemo and surgery, have good organ function, not be pregnant or breastfeeding, agree to use contraception, and have a normal heart ejection fraction. Excluded are those on other trials, with inflammatory/unresectable/metastatic breast cancer, allergies to similar drugs/vaccine components, immune deficiencies requiring suppressants, unable to undergo apheresis or with uncontrolled illnesses.

Inclusion Criteria

I agree to use birth control or abstain from sex during the study.

My organs and bone marrow are functioning normally.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

My breast cancer cannot be surgically removed or has spread from where it started.

I have an immune deficiency or take drugs to suppress my immune system.

I am not allergic to the study vaccine or similar chemotherapy drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead In Phase

Participants receive DC vaccine at dose level 1 or 2 once per week for 6 weeks

6 weeks

Expansion Phase

Additional participants are enrolled to assess pathologic response and immunogenicity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• HER-2 pulsed DC1
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The study tests if adding a Dendritic Cell (DC1) vaccine to standard pre-surgery therapy (Paclitaxel/Trastuzumab/Pertuzumab) benefits patients with HER2+ breast cancer. Participants will receive this combination before their main treatment which includes resection surgery.

How Is the Trial Designed?

Group I: Lead In: Dose Level 2 Experimental Treatment 5 Interventions

Six participants will be treated at dose level 2: DC vaccine given at the dose of 100 million once per week for 6 weeks

Group II: Lead In - Dose level 1 Experimental Treatment 5 Interventions

Six participants will be treated at dose level 1: DC vaccine given at the dose of 50 million once per week for 6 weeks

Group III: Expansion -Estrogen Receptor (ER) positive Experimental Treatment 5 Interventions

An additional 24 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase).

Group IV: Expansion -Estrogen Receptor (ER) negative Experimental Treatment 5 Interventions

An additional 23 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase).

Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

ImmunoRestoration

Industry Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

In a study of 55 women with HER2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab with chemotherapy resulted in a median progression-free survival (PFS) of 10 months, indicating significant efficacy in this treatment approach.

The treatment was generally safe, with common side effects including neutropenia (40%), leukopenia (34.5%), and thrombocytopenia (32.7%), but serious adverse reactions were relatively low, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab plus pertuzumab in combination with chemotherapy in metastatic HER2-positive breast cancer: a retrospective single-armed cohort study in China. Qian, Y., Peng, Y., Zhou, H., et al.[2022]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

A comprehensive analysis of 14,707 adverse events related to pertuzumab from the FDA Adverse Event Reporting System revealed significant safety concerns, including potential risks of myelosuppression, cardiotoxicity, and other serious conditions occurring in 12 organ systems.

Most adverse events, particularly cardiac-related issues, were reported within the first month of therapy, highlighting the need for careful monitoring and preparedness for emergency interventions, especially in elderly patients and those with pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). Zou, SP., Yang, HY., Ouyang, ML., et al.[2023]

In the TRAIN-2 study involving 110 patients with HER2-positive breast cancer, the addition of pertuzumab to chemotherapy regimens resulted in neutropenia as the most common hematologic toxicity, affecting 53% of patients in the FEC-T arm and 51% in the PTC arm.

While both regimens showed manageable toxicity, the FEC-T arm had a higher incidence of asymptomatic ejection fraction decrease (24%) compared to the PTC arm (11%), and diarrhea was more common in the PTC arm (18% vs. 5%), indicating different toxicity profiles depending on the chemotherapy backbone used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study. van Ramshorst, MS., van Werkhoven, E., Honkoop, AH., et al.[2022]

In a case series of 19 patients with previously treated HER2-positive metastatic breast cancer, the combination of pertuzumab, trastuzumab, and taxane therapy resulted in a median progression-free survival of 4.1 months.

The treatment was associated with minimal adverse effects, showing only a slight decrease in left ventricular ejection fraction (-1%) and no occurrences of neutropenic fever, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination pertuzumab, trastuzumab, and taxane for metastatic breast cancer after first progression: a single institution's experience. Dao, BD., Ho, H., Quintal, LN.[2016]

The Her2-plasmid DNA vaccine, administered alongside GM-CSF and IL-2, was found to be safe and well-tolerated in patients with metastatic Her2-expressing breast cancer, with no acute toxicity or autoimmune reactions observed.

The vaccine successfully induced long-lasting Her2-specific antibody production in some patients, demonstrating its potential to stimulate an immune response against breast cancer, even though immediate T-cell responses were not significantly observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. Norell, H., Poschke, I., Charo, J., et al.[2023]

In a study of 210 patients with ERBB2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab without chemotherapy showed a 24-month overall survival rate of 79.0%, which is comparable to 78.1% for those receiving the combination with chemotherapy.

Patients receiving the chemotherapy-free regimen had a median progression-free survival of 8.4 months, significantly shorter than the 23.3 months for those who received chemotherapy, but the absence of chemotherapy resulted in fewer adverse events and slight improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Huober, J., Weder, P., Ribi, K., et al.[2023]

In a study of 152 patients with HER2-positive metastatic breast cancer, the combination of taxanes with trastuzumab and pertuzumab showed a significant progression-free survival (PFS) advantage over vinorelbine in patients with newly diagnosed metastatic disease, indicating a potential benefit for this specific group.

Overall, there was no significant difference in overall survival (OS) between the two treatment groups, suggesting that both taxanes and vinorelbine are viable options when combined with trastuzumab and pertuzumab for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. Reinhorn, D., Kuchuk, I., Shochat, T., et al.[2021]

In a phase III trial involving patients with high-risk HER2-positive early breast cancer, the addition of atezolizumab to standard treatment (pertuzumab-trastuzumab and chemotherapy) did not significantly improve the rates of pathologic complete response (pCR) compared to placebo, with pCR rates being 62.7% for placebo and 62.4% for atezolizumab in the overall population.

While the safety profile of atezolizumab was consistent with previous studies, it was associated with a higher frequency of serious adverse events, including five grade 5 adverse events, indicating a need for careful consideration of its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. Huober, J., Barrios, CH., Niikura, N., et al.[2022]

A phase I trial involving 22 women with HER2+ breast cancer showed that a degenerate HER2 epitope-based vaccine was well tolerated and successfully induced strong T-cell immunity in 68% to 88% of patients, with 90% generating T cells that recognized HER2 antigens.

The vaccine not only enhanced T-cell responses but also increased HER2-specific antibodies, and the immunity appeared to be sustained for at least 2 years, suggesting potential for improved outcomes when combined with trastuzumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine. Knutson, KL., Block, MS., Norton, N., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5967360/

Restoring anti-oncodriver Th1 responses with dendritic cell ... Vaccines consisting of HER2-pulsed type I polarized dendritic cells (DC1) administered during ductal carcinoma in situ and early IBC can efficiently correct ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/23/12/2961/80018/Dendritic-Cell-Vaccination-Enhances-Immune

Dendritic Cell Vaccination Enhances Immune Responses and ... Abstract. Purpose: Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223004730

Dendritic cell vaccines in breast cancer In this review, we summarize the immunomodulatory effects and related mechanisms of DC vaccine in breast cancer as well as the progress of clinical trials.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-03214

A Vaccine (Dendritic Cell 1) for the Treatment of Patients ... This phase II trial studies the side effects and best dose of dendritic cell (DC1) vaccine in treating patients with HER-2 positive breast cancer.

5. jitc.bmj.com jitc.bmj.com/content/10/6/e004841

Intratumoral delivery of dendritic cells plus anti-HER2 ... 23 An experimental HER2 peptide-pulsed type 1 polarized dendritic cell (HER2-DC1) vaccine strongly restored anti-HER2 Th1 immune response in ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02061423/

Clinical Trial: NCT02061423 The primary goals of this trial will be to determine the safety and immune activity of HER-2 pulsed DC1 vaccine in patients with high risk HER- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3241864/

A novel dendritic cell-based immunization approach for the ... These data show even in the presence of early breast cancer such DC1 are potent inducers of durable type I-polarized immunity.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03387553

NCT03387553 | HER2 Directed Dendritic Cell Vaccine ... The purpose of this study is to learn more about how to treat patients with HER-2/neu positive invasive breast cancer (IBC).