Dendritic Cell Vaccine + Pembrolizumab for Brain Metastasis from Breast Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Symptomatic brain metastases, Active autoimmune, Active infection, Hepatitis B/C, 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: 3

Duration: 6 weeks

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for breast cancer that has spread to the brain. It combines a dendritic cell vaccine (Anti-HER2/HER3 Dendritic Cell Vaccine), which boosts the immune system to fight cancer, with pembrolizumab, a drug that helps the immune system attack cancer cells. The goal is to determine if this combination can shrink brain tumors in patients with triple-negative or HER2-positive breast cancer. Patients with breast cancer that has metastasized to the brain and have untreated brain tumors 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 people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if your disease has progressed in the central nervous system, you may continue certain treatments like Her2 directed antibody treatment, aromatase inhibitors, tamoxifen, capecitabine, eribulin, or paclitaxel while on the study, as per the investigator's discretion.

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

Research has shown that the anti-HER2/HER3 dendritic cell vaccine is generally safe based on early studies. One study found the vaccine well-tolerated, with manageable side effects. Patients mostly experienced mild symptoms like tiredness or a slight fever, common with vaccines.

For pembrolizumab, many studies have confirmed its safety, even for patients with challenging conditions like cancer that has spread to the brain. Most patients experienced mild to moderate side effects, such as fatigue, itching, or a rash, typical for treatments that enhance immune system function.

Both treatments have undergone testing, and their side effects are usually manageable, making them generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of the anti-HER2/HER3 dendritic cell vaccine and pembrolizumab because it offers a new way to tackle brain metastasis from breast cancer. Unlike traditional treatments like surgery, radiation, or chemotherapy, which can have broad effects, this approach uses the body's immune system to specifically target cancer cells. The dendritic cell vaccine trains the immune system to recognize and attack HER2/HER3 proteins on the cancer cells, while pembrolizumab, an immunotherapy drug, helps keep the immune response active. This targeted strategy could lead to more effective treatments with fewer side effects.

What evidence suggests that this trial's treatments could be effective for brain metastasis from breast cancer?

Research has shown that vaccines targeting specific proteins, HER2 and HER3, may help the immune system identify and destroy cancer cells. In earlier studies, over 30% of patients with breast cancer that spread to the brain showed improvement with this treatment. In this trial, participants will receive the anti-HER2/HER3 dendritic cell vaccine alongside Pembrolizumab, a drug that helps the immune system fight cancer. Studies have found that about 42% of patients with brain metastases benefited from Pembrolizumab, experiencing positive effects inside the skull. Together, these treatments aim to strengthen the body's natural defenses against cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Sheheryar Kabraji, BMBCh

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for women with triple negative or HER2+ breast cancer that has spread to the brain. Participants must not be pregnant, agree to use birth control, and can have had certain prior treatments. They should have a life expectancy over 3 months and good organ function.

Inclusion Criteria

I last used checkpoint inhibitors 3 weeks ago or more.

I can continue certain treatments if my breast cancer has spread to my brain.

I am not pregnant or breastfeeding and follow the study's birth control requirements.

Exclusion Criteria

I have an active hepatitis B or C infection.

My illness is quickly getting worse, which may stop me from getting all vaccine doses.

I have not had a stroke or mini-stroke in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-HER2/HER3 dendritic cell vaccine intradermally on days 1, 22, and 43, and Pembrolizumab intravenous infusion on the same days

6 weeks

3 visits (in-person)

Maintenance

Participants receive pembrolizumab IV over 30 minutes on day 1 of each cycle, with cycles repeating every 21 days for up to 2 years. Booster doses of anti-HER2/HER3 dendritic cell vaccine may be given every 3-6 months

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-HER2/HER3 Dendritic Cell Vaccine
• Pembrolizumab

Trial Overview The trial tests dendritic cell vaccines targeting Her2/Her3 combined with pembrolizumab, an immune checkpoint inhibitor. The goal is to see if this combination can shrink brain metastases from breast cancer by enhancing the body's immune response.

How Is the Trial Designed?

Group I: Treatment (anti-HER2/3 dendritic cell vaccine) Experimental Treatment 2 Interventions

TREATMENT PHASE: Patients receive anti-HER2/HER3 dendritic cell vaccine ID on days 1, 22, and 43. Patients will also receive pembrolizumab IV on the same days. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive a booster dose of anti-HER2/3 dendritic cell vaccine ID, every 3-6 months in the opinion of principal investigator.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a study using mouse models, dendritic cells modified to express the HER-2/neu antigen (DC(neu)) were found to elicit stronger immune responses against breast cancer compared to a DNA-based vaccine, leading to complete protection from tumor challenges.

The DC(neu) vaccine not only enhanced immune responses but also significantly delayed breast cancer development in transgenic mice, indicating its potential as a more effective immunotherapeutic approach for targeting HER-2/neu in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER-2/neu-gene engineered dendritic cell vaccine stimulates stronger HER-2/neu-specific immune responses compared to DNA vaccination. Chan, T., Sami, A., El-Gayed, A., et al.[2012]

In a phase 2 trial involving 36 patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC), pembrolizumab demonstrated activity, achieving a brain metastasis response in 22% of melanoma patients and 33% of NSCLC patients, with responses being durable for most.

The treatment had an acceptable safety profile, with serious adverse events occurring in a small percentage of patients, indicating that systemic immunotherapy could be a viable option for those with untreated or progressive brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Goldberg, SB., Gettinger, SN., Mahajan, A., et al.[2022]

A patient with brain metastases experienced mental status changes and MRI findings of lesion enlargement after receiving pembrolizumab, an immunotherapy drug, indicating a potential adverse effect of treatment in the central nervous system.

Histological analysis showed that the observed changes were due to pseudoprogression, characterized by tumor cell clusters and inflammatory responses, highlighting the need for careful monitoring and possible immune suppression in patients undergoing immunotherapy for brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. Cohen, JV., Alomari, AK., Vortmeyer, AO., et al.[2022]

A new protein vaccine targeting breast cancer delivers HER2 to dendritic cells in the body, which is a promising method for stimulating the immune system.

This approach has shown potential to create long-lasting and comprehensive immunity against breast cancer, suggesting it could be an effective treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting dendritic cells in situ for breast cancer immunotherapy. Wang, B.[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]

The DEC-HER2 fusion antibody vaccine effectively induced strong T cell and B cell immunity against the HER2 antigen in a mouse model, demonstrating its potential as a breast cancer vaccine.

Mice immunized with the DEC-HER2 vaccine showed significant protection against neu-expressing mammary tumors, with both CD4+ and CD8+ T cells playing crucial roles in this tumor protection, indicating a promising strategy for future breast cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice. Wang, B., Zaidi, N., He, LZ., et al.[2021]

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]

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]

In a study of 186 breast cancer patients, those vaccinated with the E75 + GM-CSF vaccine showed a lower recurrence rate (8.3%) compared to the control group (14.8%), although this difference was not statistically significant (P = 0.17).

Vaccinated patients who did experience recurrences had more aggressive disease characteristics, such as higher tumor grades and nodal stages, but they exhibited similar immune responses to the vaccine as those who did not recur, suggesting that the vaccine may still provide some protective benefits against more aggressive forms of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Amin, A., Benavides, LC., Holmes, JP., et al.[2020]

Immunizations using dendritic cells (DCs) loaded with HER2 tumor antigens were found to be safe, with no toxicities reported in patients with high-risk breast cancer or metastatic cancers expressing HER2.

In a pilot study, patients receiving DCs loaded with the HER2 intracellular domain showed promising results, with all three patients having no recurrence of cancer for up to 2.5 years, indicating potential efficacy in preventing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2 dendritic cell vaccines. Morse, MA., Clay, TM., Colling, K., et al.[2019]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II clinical trial involving 23 melanoma patients with untreated brain metastases, pembrolizumab demonstrated a 26% response rate in brain metastases, indicating its potential efficacy in this challenging patient population.

The treatment was associated with acceptable toxicity, as 65% of patients experienced neurologic adverse events, mostly mild (grade 1 or 2), and nearly half of the patients (48%) were alive at 24 months, suggesting durable responses and a need for careful management of brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Kluger, HM., Chiang, V., Mahajan, A., et al.[2020]

In a phase 2 trial involving 42 patients with untreated brain metastases from non-small-cell lung cancer (NSCLC), pembrolizumab showed a 29.7% response rate in patients with PD-L1 expression of at least 1%, indicating its efficacy in treating brain metastases.

The treatment was generally safe, with serious adverse events occurring in 14% of patients, but no treatment-related deaths were reported, suggesting that pembrolizumab can be a viable option for selected patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Goldberg, SB., Schalper, KA., Gettinger, SN., et al.[2021]

Citations

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NCT04348747 | Dendritic Cell Vaccines Against Her2/Her3 ... This phase IIa trial studies how well dendritic cell vaccines against Her2/Her3 and pembrolizumab work for the treatment of triple negative breast cancer or ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS1112

Phase IIa study of αDC1 vaccines targeting HER2/HER3 ... Background: Brain metastases develop in up to 50% patients (pts) with metastatic triple negative breast cancer (TNBC) and HER2+ BC, constituting ...

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Dendritic Cell Vaccines against Her2/Her3 for the ... This phase I trial tests the safety, side effects, and best dose of dendritic cell vaccines against Her2/Her3 in treating patients with triple negative breast ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11477856/

Breast Cancer Brain Metastasis: A Comprehensive Review Over 30% of patients with BMs from breast cancer experienced improvement after receiving this combination treatment, whereas another 16% ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0305737224001142

Long road towards effective HER3 targeting in breast cancer The results showed that HER3 2+/3+ was expressed in 91% of brain metastasis, higher than in primary tumors (59 %) and HER3 was observed in brain metastases for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8716407/

Phase I Clinical Trial of an Autologous Dendritic Cell ... The AdHER2 DC vaccine showed evidence of immunogenicity and preliminary clinical benefit in patients with HER2-expressing cancers, along with an ...

7. jhoponline.com jhoponline.com/issue-archive/2023-issues/june-2023-vol-13-no-3/anti-her2-her3-dc1-vaccines-plus-pembrolizumab-for-brain-metastases-in-patients-with-triple-negative-or-her2-positive-breast-cancer

Anti-HER2/HER3 αDC1 Vaccines Plus Pembrolizumab for ... Up to 50% of patients with metastatic triple-negative breast cancer and HER2-positive breast cancer will have brain metastases, ...