T-Cell Therapy + Vaccine + Pepinemab/Trastuzumab for Breast Cancer

Overseen By Kim Sprenger

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Trastuzumab

Must not be taking: Corticosteroids, others

Disqualifiers: Brain metastases, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for people with HER2 positive breast cancer, including a vaccine, a protein called pepinemab, and T-cell therapy (a type of personalized immune treatment). The goal is to determine if this combination is safe when added to trastuzumab, a standard breast cancer treatment. Participants will receive varying doses to identify the safest and most effective one. This trial may suit those who have experienced HER2 positive breast cancer progression despite trastuzumab and have undergone up to three prior chemotherapy treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 14 days before starting the trial, and you cannot be on other investigational agents within 14 days or 5 half-lives before starting the trial.

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

Research has shown that the treatments in this trial are generally safe based on previous studies.

The Dendritic Cell (DC1) vaccine showed promise in earlier research. Studies found it to be safe, with few serious side effects. Participants usually did not experience the severe side effects often seen with chemotherapy or radiation.

Pepinemab, another treatment in the trial, also has a strong safety record. Multiple studies have reported that it is well-tolerated and safe for both cancer and neurological conditions.

Adoptive T-Cell therapy, the third treatment in this trial, is still under study. It is considered a promising way to help the immune system fight cancer. While more information is needed, past research has not shown major safety concerns.

As this is an early-phase trial, the main goal is to further assess the safety of these treatments together. This phase ensures that treatments are safe before testing their effectiveness on a larger scale. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which often include chemotherapy, hormone therapy, or HER2-targeted drugs like trastuzumab, this investigational approach combines dendritic cell (DC1) vaccines, pepinemab, and T-cell therapy to potentially enhance the body's immune response. Researchers are excited about this treatment because it targets the cancer in a multi-pronged manner: the DC1 vaccine is designed to train the immune system to recognize and attack cancer cells more effectively, while pepinemab aims to disrupt the tumor's ability to suppress the immune response. The T-cell therapy further supercharges this attack by using modified T-cells that are specifically expanded to target HER2-positive cancer cells, potentially offering a more personalized and robust defense against the cancer.

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

This trial will test the combination of T-Cell therapy, the Dendritic Cell (DC1) vaccine, pepinemab, and trastuzumab for breast cancer. Studies have shown that the DC1 vaccine can trigger a strong immune response against HER2-positive breast cancer, potentially reducing or eliminating cancer cells. Research indicates that pepinemab may enhance the body's immune response when combined with other cancer treatments, making it a promising addition to treatment plans. T-cell therapy, which uses the body's own immune cells to attack cancer, has shown potential in targeting and fighting hard-to-treat breast cancer types. This trial aims to determine if these treatments can work better together to fight breast cancer effectively. ^{1 3 4 6 7}

Who Is on the Research Team?

HEATHER HAN, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with HER2 positive breast cancer who have seen their disease progress while on trastuzumab and have had no more than three lines of chemotherapy for metastatic cancer. They must be in good health otherwise, not pregnant or nursing, without a history of certain viruses (HIV, Hepatitis B/C), autoimmune diseases, or recent vaccines.

Inclusion Criteria

I am using or willing to use effective birth control methods if of childbearing potential.

Must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

My breast cancer is HER2 positive and I am eligible for trastuzumab treatment.

Exclusion Criteria

I have undergone a type of cell therapy treatment before.

I am not pregnant or nursing.

I do not have any serious illnesses that could interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 weekly injections of dendritic cell (DC1) vaccines in combination with trastuzumab and pepinemab

6 weeks

T-Cell Therapy

Blood is collected for T-cell therapy, and patients are treated with IL-15 Expanded HER2 specific CD4+ Th1 cells

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Dendritic Cell (DC1) Vaccine
• Pepinemab
• T-Cell therapy
• Trastuzumab

Trial Overview The study tests Adoptive T-Cell therapy after a Dendritic Cell vaccine combined with pepinemab and standard trastuzumab treatment. It aims to improve outcomes for those with advanced HER2 positive breast cancer by enhancing the body's immune response.

How Is the Trial Designed?

Group I: T-Cell therapy dose level 3 Experimental Treatment 4 Interventions

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with IL-15 Expanded HER2 specific CD4+ Th1 cell .5-2.5 x 10\^9, IL-7 and Expanded HER2 specific CD4+ Th1 cell .5-2.5 x 10\^9.

Group II: T-Cell therapy dose level 2 Experimental Treatment 4 Interventions

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with IL-15 Expanded HER2 specific CD4+ Th1 cell .25-1.2 x 10\^9, IL-7 and Expanded HER2 specific CD4+ Th1 cell .25-1.2 x 10\^9.

Group III: T-Cell therapy dose level 1 Experimental Treatment 4 Interventions

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with IL-15 Expanded HER2 specific CD4+ Th1 cell 0.5.0-2.5 x 10\^8, IL-7 and Expanded HER2 specific CD4+ Th1 cell 0.5.0-2.5 x 10\^8.

Group IV: T Cell therapy dose expansion Experimental Treatment 4 Interventions

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with CD4 treated t-cells at the maximum tolerated dose determined.

Dendritic Cell (DC1) Vaccine is already approved in United States for the following indications:

Approved in United States as Sipuleucel-T (a different dendritic cell vaccine, not DC1 specifically) for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Vaccinex Inc.

Industry Sponsor

Trials

12

Recruited

740+

Published Research Related to This Trial

In a phase 1 trial involving 66 patients with advanced ERBB2-positive breast cancer, a 100-μg dose of a plasmid-based vaccine successfully generated ERBB2-specific type 1 T cells in most participants, indicating its potential efficacy in enhancing immune response after trastuzumab therapy.

The vaccine was generally safe, with most side effects being mild (grade 1 and 2), and the highest dose was linked to greater persistence of plasmid DNA at the injection site, suggesting a longer-lasting immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Outcomes of a Plasmid DNA Vaccine Encoding the ERBB2 Intracellular Domain in Patients With Advanced-Stage ERBB2-Positive Breast Cancer: A Phase 1 Nonrandomized Clinical Trial. Disis, MLN., Guthrie, KA., Liu, Y., et al.[2023]

The HER2 peptide-pulsed DC1 vaccination was found to be safe and well-tolerated among 54 HER2-positive patients, with no significant differences in immune response rates across different injection methods (intralesional, intranodal, or both).

Patients with ductal carcinoma in situ (DCIS) showed a higher pathologic complete response (pCR) rate compared to those with early invasive breast cancer (IBC), suggesting that the immune response in sentinel lymph nodes may be a better indicator of treatment effectiveness than peripheral blood responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial. Lowenfeld, L., Mick, R., Datta, J., et al.[2022]

In a study involving 13 patients with HER-2/neu positive ductal carcinoma in situ (DCIS), a dendritic cell vaccine targeting HER-2/neu led to significant immune responses, with 85% of patients developing CD4+ T cells and 80% developing CD8+ T cells that recognized breast cancer cells.

Post-vaccination, many patients exhibited reduced HER-2/neu expression in tumor samples, indicating that the vaccine may effectively induce an immune response capable of 'immunoediting' tumor cells, suggesting its potential for both prevention and treatment of early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Czerniecki, BJ., Koski, GK., Koldovsky, U., et al.[2021]

In a preclinical model of HER2+ breast cancer, vaccination with class II HER2-pulsed dendritic cells (DC1) led to increased infiltration of both CD4 and CD8 T cells in tumors, resulting in delayed tumor growth and improved survival.

Combining class II HER2-DC1 with anti-PD-1 therapy significantly enhanced anti-tumor efficacy, suggesting that this combination could be a promising treatment strategy for patients with metastatic HER2 breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Anti-PD1 Therapy Following Dendritic Cell Vaccination Improves Survival in a HER2 Mammary Carcinoma Model and Identifies a Critical Role for CD4 T Cells in Mediating the Response. Kodumudi, KN., Ramamoorthi, G., Snyder, C., et al.[2023]

The combination of dendritic cell vaccination with trastuzumab and vinorelbine was found to be safe for patients with HER2-overexpressing and nonoverexpressing metastatic breast cancer, with only one patient experiencing significant toxicity and no deaths reported.

While 46% of patients achieved stable disease and some immune responses were generated, these immune responses did not consistently correlate with clinical outcomes, although one patient demonstrated a strong immune response and has survived over 14 years post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a Dual-Epitope Dendritic Cell Vaccine as Part of Combined Immunotherapy for HER2-Expressing Breast Tumors. Vincent, BG., File, DM., McKinnon, KP., et al.[2023]

The combination of the GP2 + GM-CSF vaccine with trastuzumab was found to be safe in a trial involving 17 disease-free HER2-positive breast cancer patients, with no significant toxicities observed and stable heart function throughout the study.

The vaccine successfully stimulated an immunologic response, as indicated by an increase in local reaction size and a trend towards higher interferon-γ responses, suggesting potential effectiveness in enhancing anti-tumor immunity when used alongside trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Phase Ib Trial of Combination Immunotherapy with a CD8+ T Cell Eliciting Vaccine and Trastuzumab in Breast Cancer Patients. Clifton, GT., Litton, JK., Arrington, K., et al.[2021]

Intratumoral delivery of HER2-pulsed dendritic cells combined with anti-HER2 antibodies led to complete tumor regression in 75-80% of treated mice, significantly enhancing immune cell infiltration compared to subcutaneous delivery and standard chemotherapy.

This approach not only induced strong anti-HER2 immune responses but also provided lasting immunity that prevented secondary tumor formation, suggesting it could be a promising alternative to traditional chemotherapy for HER2 positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral delivery of dendritic cells plus anti-HER2 therapy triggers both robust systemic antitumor immunity and complete regression in HER2 mammary carcinoma. Ramamoorthi, G., Kodumudi, K., Snyder, C., 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]

In a study of 60 HER2+ breast cancer patients, those who received HER2-derived peptide vaccines after trastuzumab treatment showed no cancer recurrences over a median follow-up of more than 34 months, indicating a potential improvement in disease-free survival.

Trastuzumab enhances the immune response by facilitating the uptake of HER2 by dendritic cells, leading to increased activation of T cells specific to the HER2 peptide, which may explain the observed synergy between the vaccine and trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Increases HER2 Uptake and Cross-Presentation by Dendritic Cells. Gall, VA., Philips, AV., Qiao, N., et al.[2021]

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