Elacestrant + DC1 Vaccines for Breast Cancer

Overseen By Taylor Lewis Whann

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Elacestrant, Immunosuppressants, Cytotoxic chemotherapy, others

Disqualifiers: Pregnancy, CNS metastases, Active infection, others

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

Compensation: Varies

Number of Visits: 11

Duration: 8 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for patients with hormone-positive, HER2-negative metastatic breast cancer. It combines a novel vaccine approach using DC1 vaccines (targeting native/mutated ESR1) with elacestrant, a medication already used for this cancer type. The trial aims to determine the safety and feasibility of this combination. Individuals diagnosed with this specific type of breast cancer, particularly those with an ESR1 mutation who have tried other treatments, might be suitable for this study. 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 novel combination therapy.

Will I have to stop taking my current medications?

The trial requires a 14-day period without certain cancer treatments, like chemotherapy, hormone therapies, and targeted agents, before starting the study. If you're on these medications, you'll need to stop them for two weeks before joining the trial.

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

Research has shown that elacestrant is already approved by the FDA for treating certain types of breast cancer. This approval confirms its safety and effectiveness for patients with this condition. In studies, elacestrant helped patients live longer without their cancer worsening and was found to be safe, with manageable side effects.

Regarding the DC1 vaccine, research suggests that using it with elacestrant could be safe and tolerable, as patients did not experience many severe side effects when taking both together. The DC1 vaccine is designed to enhance the body's immune response against cancer cells.

Overall, while specific data is still being collected, the treatments in this study appear to have a safety record that supports further research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Elacestrant and DC1 vaccines for breast cancer because it introduces a novel way to tackle the disease. Unlike standard treatments like hormonal therapies or chemotherapy, this approach uses personalized DC1 vaccines that are pulsed with specific peptides from estrogen receptor mutations. This targets the cancer more precisely. Elacestrant, an oral selective estrogen downregulator, is already known to be effective for ESR1 mutated breast cancer, but when combined with the DC1 vaccine, it could potentially enhance the immune system's ability to fight cancer. This dual approach not only targets cancer cells directly but also stimulates the patient's immune response, offering a promising new strategy in the fight against metastatic breast cancer.

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

Research shows that elacestrant is approved for treating ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer. It has been proven to slow cancer progression. In this trial, participants will receive a combination of elacestrant with the DC1 vaccine. Studies suggest that this combination might be safe and could enhance treatment efficacy. The DC1 vaccine aids the immune system in attacking cancer cells. Early results indicate that this combination might help break down ESR1, a protein that promotes cancer growth. Overall, promising evidence suggests this treatment could effectively manage this type of breast cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Aixa E Soyano Muller, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with hormone-positive, HER2-negative metastatic breast cancer. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be required to have a particular status of disease progression.

Inclusion Criteria

I've been treated with hormone therapy and a CDK 4/6 inhibitor for my advanced cancer.

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so on my behalf.

My breast cancer is hormone positive, HER2 negative, and confirmed by a biopsy.

Exclusion Criteria

My cancer has spread to my brain or spinal cord and is getting worse.

Inability to comply with protocol requirements

History of allergic reactions attributed to the study drugs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DC1 vaccines and elacestrant. DC1 vaccines are administered weekly for eight consecutive weeks, alternating between native and mutated ESR1 DC1s. Elacestrant is administered concurrently and continued after.

8 weeks

8 visits (in-person)

Induction

Pulsed DC1 vaccines are administered every four weeks for three doses after initial induction.

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression-free survival and overall response rate.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• DC1 native/mutated ESR1
• Elacestrant

Trial Overview The study is testing the combination of a Dendritic Cell (DC1) vaccine targeting mutated ESR1 receptors and elacestrant, a drug for treating breast cancer. It aims to assess the safety and how doable this approach is for patients.

How Is the Trial Designed?

Group I: Elacestrant + DC1 Experimental Treatment 2 Interventions

Patients will undergo apheresis of peripheral blood to collect and create DC1 vaccines. DC1 will be pulsed with ESR1 native or mutated peptides. After DC1 vaccines have undergone safety testing and are ready to be used, patients will be injected in groin nodes (or accessible breast tumor if available) weekly with these pulsed DC1 for eight consecutive weeks. They will alternate between native ESR1 DC1s and mutated ESR1 DC1s. Patients will receive combination of DC1 vaccinations and Elacestrant concurrently. Elacestrant is a novel oral selective estrogen downregulator, administered during vaccination and continued after. Elacestrant is considered standard of care for patients with ESR1 mutated HR+ HER2-metastatic breast cancer. Pulsed DC1 will be administered after initial induction every four weeks x 3 doses.

DC1 native/mutated ESR1 is already approved in United States for the following indications:

Approved in United States as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

The V Foundation for Cancer Research

Collaborator

Trials

21

Recruited

1,300+

Published Research Related to This Trial

A dendritic cell vaccine targeting the ErbB-2/neu oncogene showed protective immunity in about 60% of tested mice, indicating its potential as a therapeutic strategy for breast cancer.

The vaccine's effectiveness was enhanced when combined with IL-12, demonstrating that optimizing immune responses through cytokine co-delivery can improve treatment outcomes against tumors that overexpress ErbB-2/neu.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12. Chen, Y., Emtage, P., Zhu, Q., et al.[2019]

Breast cancer has a more significant immune response than previously thought, with tumor-associated antigens (TAA) identified as potential targets for immunotherapy, despite the presence of inhibitory factors that weaken this response.

Dendritic cells (DCs) play a crucial role in bridging the immune system and breast cancer, and while clinical trials on DC vaccination are still limited, there is growing evidence supporting its potential effectiveness in enhancing the immune response against breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immune response to breast cancer, and the case for DC immunotherapy. Allan, CP., Turtle, CJ., Mainwaring, PN., et al.[2008]

An autologous dendritic cell (DC) vaccine developed for breast cancer showed promising in vitro efficacy, eliciting a strong cytotoxic T-lymphocyte response against autologous breast cancer cells in 12 female patients with early-stage disease.

The matured DCs demonstrated significant upregulation of activation markers and produced high levels of the cytokine IL12-p70, indicating their potential effectiveness in stimulating the immune response, and they maintained viability and safety after cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells. Tomasicchio, M., Semple, L., Esmail, A., et al.[2020]

Dendritic cell (DC) vaccines have shown considerable anti-tumor effects in breast cancer treatment, with some already in clinical trials, highlighting their potential as a promising immunotherapy option.

This review discusses the immunomodulatory effects and mechanisms of DC vaccines, suggesting that while they offer new avenues for treatment, there are still challenges to overcome in their development and application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccines in breast cancer: Immune modulation and immunotherapy. Qian, D., Li, J., Huang, M., et al.[2023]

The MTDH/AEG-1 DNA vaccine, delivered via attenuated Salmonella typhimurium, effectively triggered strong immune responses against breast cancer, showing significant anti-tumor and anti-metastatic effects in mouse models.

In addition to its preventive capabilities, the vaccine enhanced the effectiveness of the chemotherapy drug doxorubicin, increasing chemosensitivity and prolonging survival in tumor-bearing mice without notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer. Qian, BJ., Yan, F., Li, N., et al.[2020]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS1132

Immunologic targeting of native and mutated ESR1 ... Combining DC1 vaccination with novel endocrine therapies such as Elacestrant, we expect an increase in ESR1 degradation and enhanced antigen ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09583

A Dendritic Cell Vaccine in Combination with Elacestrant ... Giving the DC1 vaccine in combination with elacestrant may be safe, tolerable and/or effective in treating patients with HR+, HER2 negative metastatic breast ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11443208/

Elacestrant in ER+, HER2− Metastatic Breast Cancer with ... Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety versus standard-of-care (SOC) endocrine therapy (ET)

4. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer

FDA approves elacestrant for ER-positive FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer.

5. orserdu.com orserdu.com/

ESR1-Mutated ER+/HER2 mBC Treatment - ORSERDU ... Evaluate ORSERDU®, a treatment option for ESR1-mutated, ER+/HER2-advanced or metastatic breast cancer following disease progression on endocrine therapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06691035

NCT06691035 | Immunologic Targeting of ESR1 Receptor ... Elacestrant is considered standard of care for patients with ESR1 mutated HR+ HER2-metastatic breast cancer. Pulsed DC1 will be administered after initial ...