Dendritic Cell Vaccine + Pembrolizumab for Brain Metastasis from Breast Cancer

Recruiting at 2 trial locations

Overseen by Sheheryar Kabraji, BMBCh

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial studies a treatment combining a vaccine and a drug to boost the immune system in patients with aggressive breast cancer that has spread to the brain. The vaccine helps the immune system recognize cancer cells, while the drug enhances its ability to fight them.

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.

What data supports the effectiveness of the treatment Dendritic Cell Vaccine + Pembrolizumab for Brain Metastasis from Breast Cancer?

Research shows that targeting dendritic cells with a HER2 protein vaccine can induce a strong immune response against breast cancer in mice, and similar vaccines have shown promise in generating immune responses in patients with HER2-expressing breast tumors. This suggests potential effectiveness for the dendritic cell vaccine component of the treatment. ^{1 2 3 4 5}

Is the Dendritic Cell Vaccine + Pembrolizumab treatment safe for humans?

Research on dendritic cell vaccines targeting HER2 in breast cancer patients shows that these vaccines are generally safe, with minimal side effects reported. In studies, patients tolerated the treatment well, with most side effects being mild (grade 1/2), and no serious toxicities were observed. ^{1 3 6 7 8}

How is the dendritic cell vaccine with pembrolizumab treatment different for brain metastasis from breast cancer?

This treatment is unique because it combines a dendritic cell vaccine, which helps the immune system recognize and attack cancer cells, with pembrolizumab, a drug that blocks a pathway (PD-1) used by cancer cells to hide from the immune system. This combination aims to enhance the body's ability to fight cancer, especially in the brain, where traditional treatments may not be as effective. ^{9 10 11 12 13}

Research Team

Sheheryar Kabraji, BMBCh

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Anti-HER2/HER3 Dendritic Cell Vaccine (Cancer Vaccine)
• Pembrolizumab (PD-1/PD-L1 Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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]

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]

References

1. England 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. [2021]

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

Targeting dendritic cells in situ for breast cancer immunotherapy. [2021]

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

Efficacy of a Dual-Epitope Dendritic Cell Vaccine as Part of Combined Immunotherapy for HER2-Expressing Breast Tumors. [2023]

4. England 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. [2012]

5. Germany 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. [2020]

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

HER2 dendritic cell vaccines. [2019]

7. Netherlands 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. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. [2020]

12. England 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. [2021]

13. England 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. [2022]