Vaccine + Chemotherapy + Monoclonal Antibody Therapy for Breast Cancer

Overseen By Jennifer Childs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Chemotherapy, HER2-targeted therapy

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiomyopathy, Autoimmune disease, HIV, others

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

Duration: 12 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the immunologic response and side effects of using the WOKVAC vaccine in combination with chemotherapy and HER2-targeted monoclonal antibody therapy before surgery in treating patients with breast cancer. Vaccines like WOKVAC are made from tumor-associated antigens which may help the body build an effective immune response to kill tumor cells. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are forms of targeted therapy because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab and pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving the WOKVAC vaccine at the same time (concurrently) with paclitaxel, trastuzumab, and pertuzumab before surgery may kill more tumor cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using immunosuppressive agents or systemic corticosteroids, you may need to stop, as these are not allowed in the trial.

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

Research shows that combining trastuzumab (Herceptin) with chemotherapy and pertuzumab is effective for treating HER2-positive breast cancer. Additionally, studies in mice suggest that a DNA vaccine targeting HER2/neu, when combined with trastuzumab, can lead to significant tumor regression. ^{1 2 3 4 5}

Is the combination of vaccine, chemotherapy, and monoclonal antibody therapy for breast cancer safe?

The combination of trastuzumab and pertuzumab with chemotherapy has been studied for safety in breast cancer treatment. Some studies report increased toxicity (side effects) when pertuzumab is added, but these treatments are generally considered safe for use in humans, with specific attention to cardiac safety and other potential adverse effects. ^{5 6 7 8 9}

What makes this breast cancer treatment unique?

This treatment is unique because it combines a DNA vaccine targeting HER2 with chemotherapy and monoclonal antibodies, aiming to stimulate the immune system to produce specific antibodies and T-cells against cancer, potentially enhancing the effects of existing monoclonal therapies like Trastuzumab. ^{3 4 5 10 11}

Research Team

William Gwin

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with HER2+ stage I-III breast cancer who plan to undergo neoadjuvant therapy. They must have adequate organ function, agree to use contraception if of child-bearing potential, and not be on immunosuppressants or other investigational drugs. Exclusions include HIV-positive individuals, uncontrolled autoimmune diseases, recent major surgery, certain heart conditions, and known allergies to vaccine components.

Inclusion Criteria

I have stage I-III HER2+ breast cancer and will start treatment soon.

Your platelet count is at least 75,000 per microliter within the past 4 weeks before starting the study treatment.

Your white blood cell count is at least 500 per cubic millimeter.

Exclusion Criteria

You are allergic to the GM-CSF adjuvant.

I have not had major surgery in the last 4 weeks.

I have had hepatitis B or C but it has been treated and cleared.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive WOKVAC vaccine, paclitaxel, trastuzumab, and pertuzumab. WOKVAC is administered intradermally on day 13, paclitaxel via infusion on days 1, 8, and 15, and trastuzumab and pertuzumab intravenously on day 1. Treatment repeats for up to 4 cycles.

12 weeks

Surgery

Surgical resection of the tumor is performed after completion of the treatment cycles.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with annual follow-ups for up to 5 years.

5 years

Treatment Details

Interventions

• Paclitaxel
• Pertuzumab
• pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine
• Trastuzumab

Trial Overview The study tests the WOKVAC vaccine combined with chemotherapy (paclitaxel) and HER2-targeted monoclonal antibody therapy (trastuzumab and pertuzumab) before surgery in patients with breast cancer. The goal is to see if this combination can better stimulate the immune system to attack tumor cells compared to standard treatments alone.

Participant Groups

Group I: Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab) Experimental Treatment 4 Interventions

Patients receive WOKVAC ID on day 13. Treatment repeats for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel via infusion on days 1, 8, and 15, and trastuzumab IV and pertuzumab IV on day 1. Treatment repeats for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a mouse model of breast cancer, combining a modified HER2/neu DNA vaccine with the monoclonal antibody trastuzumab resulted in significant tumor regression, suggesting a promising new treatment strategy.

This combination therapy may enhance the efficacy of trastuzumab, which is often limited by resistance in breast cancer patients, indicating potential clinical benefits for those with HER2/neu-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of epitope-optimized DNA vaccination and passive infusion of monoclonal antibody against HER2/neu leads to breast tumor regression in mice. Orlandi, F., Guevara-Patiño, JA., Merghoub, T., et al.[2017]

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 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]

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]

Pertuzumab, a monoclonal antibody targeting HER2, significantly improves progression-free survival in patients with HER2-positive metastatic breast cancer, with a median of 18.5 months compared to 12.4 months for the placebo group, based on a phase III trial with previously untreated patients.

While the overall safety profile of pertuzumab is similar to placebo, it is associated with a higher incidence of specific side effects such as diarrhea, rash, and neutropenia, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Boix-Perales, H., Borregaard, J., Jensen, KB., 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]

The TCHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) demonstrated an acceptable safety profile in older postmenopausal women with nonmetastatic HER2-positive breast cancer, with no severe cardiac dysfunction observed.

While both TCHP and TCP regimens had similar mild toxicities, the TCHP group experienced higher rates of febrile neutropenia and hospitalization due to treatment-related toxicities, suggesting careful monitoring is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of Neoadjuvant Pertuzumab Combined with Trastuzumab in Nonmetastatic HER2-Positive Breast Cancer in Postmenopausal Elderly Women of South Asia. Hussain, N., Said, ASA., Khan, Z.[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]

The development of a protein vaccine targeting HER-2/neu aims to induce a humoral anti-tumor response, potentially enhancing the effects of existing monoclonal antibody therapies like Trastuzumab.

The vaccine has undergone extensive testing in animal models and toxicology programs, leading to its evaluation in three clinical trials involving breast cancer patients, highlighting its potential as a complementary treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on the development of a therapeutic HER-2 cancer vaccine. Renard, V., Leach, DR.[2014]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Combination of epitope-optimized DNA vaccination and passive infusion of monoclonal antibody against HER2/neu leads to breast tumor regression in mice. [2017]

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

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

3. England 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. [2023]

4. Netherlands 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. [2021]

5. United States 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. [2022]

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

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

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

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. [2023]

8. Netherlands 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. [2022]

9. Egypt pubmed.ncbi.nlm.nih.gov

Safety Assessment of Neoadjuvant Pertuzumab Combined with Trastuzumab in Nonmetastatic HER2-Positive Breast Cancer in Postmenopausal Elderly Women of South Asia. [2022]

10. England pubmed.ncbi.nlm.nih.gov

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

11. Netherlands pubmed.ncbi.nlm.nih.gov

Perspectives on the development of a therapeutic HER-2 cancer vaccine. [2014]