Dendritic Cell Vaccine for Breast Cancer

(DecipHER Trial)

Overseen By Brian J. Czerniecki, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Anthracyclines, Corticosteroids, Antineoplastics, others

Disqualifiers: Inflammatory breast cancer, Autoimmune disease, HIV/AIDS, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine to determine its effectiveness in treating certain types of breast cancer, specifically Triple Negative and HR low positive breast cancer. The vaccine uses dendritic cells, part of the immune system, to target cancer cells when combined with standard chemotherapy. The study seeks individuals diagnosed with HER2-negative breast cancer who have not received specific prior treatments, such as anthracycline-based chemotherapy. Participants should be prepared to undergo chemotherapy and standard local therapy as advised by their doctor. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational drugs or active cancer treatments. It's best to discuss your current medications with the trial team to see if they are allowed.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or active cancer treatments, and you should not be using long-term corticosteroids or have received a live vaccine within 30 days before joining the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that both HER2 and HER3 dendritic cell vaccines appear safe. Studies suggest the HER2 vaccine is well-tolerated, with participants showing a decrease in a marker linked to certain breast cancers. Early studies also found the HER3 vaccine to be well-tolerated. Although research remains in the early stages, this is promising for potential trial participants. Safety remains a primary focus, and these studies provide initial evidence that these vaccines could be a safe option alongside standard treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dendritic cell vaccines for breast cancer because they offer a novel way to target cancer cells. Unlike traditional treatments like chemotherapy and targeted therapies that can affect healthy cells and cause side effects, these vaccines harness the body's immune system to specifically target and attack cancer cells. The vaccines use HER2- and HER3-primed dendritic cells, which are designed to recognize and mount an immune response against breast cancer cells expressing these proteins. This precision could lead to more effective treatments with fewer side effects, making it a promising avenue in cancer therapy.

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

Research has shown that dendritic cell vaccines, such as those targeting HER2 and HER3, hold promise for treating breast cancer. In past studies, HER2-targeted vaccines successfully triggered strong and lasting immune responses, sometimes even reducing or eliminating signs of cancer. Early results suggest that these vaccines, when combined with other treatments, can enhance the body's ability to fight cancer cells. Initial trials for HER3-targeted vaccines indicate they may boost the immune system's response to cancer, especially alongside standard treatments. In this trial, participants will receive either HER2-primed or HER3-primed dendritic cell vaccines, with dose escalation to determine the maximum tolerated dose. Overall, these vaccines offer hope for a more personalized and focused approach to fighting breast cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Ricardo Costa, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage Triple Negative or HR low positive breast cancer, who can undergo standard chemotherapy and surgery. Participants need normal organ/marrow function, no severe autoimmune diseases, not pregnant/nursing, and no recent vaccines or other cancer treatments.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent agreement prior to study registration

Patients must have normal organ and marrow function within 14 days of registration: ANC ≥ 1500/μL, Platelets ≥ 75 000/μL, Total bilirubin ≤ 1.5 x institutional ULN (except patients with Gilbert's syndrome), AST/ALT ≤ 3 x institutional ULN, Creatinine ≤ 1.5 x institutional ULN, Left ventricular ejection fraction above institutional lower limit of normal

My tumor is either not hormone receptor positive or has low hormone receptor positivity.

Exclusion Criteria

I have no cancer history except for certain skin cancers, cervical cancer in situ, or any cancer I've been free from for 3+ years.

I have not received a live vaccine in the last 30 days.

I have been treated with a therapy targeting HER2 or HER3 before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation to determine the maximum tolerated dose (MTD) of HER2- and HER3-primed DC1 study vaccines

4 weeks

Multiple visits for dose escalation and monitoring

Treatment

Participants receive DC1 injections and standard of care chemotherapy

24 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• HER2-primed Dendritic cells
• HER3-primed Dendritic cells

Trial Overview The DecipHER Trial tests if a new vaccine made from Dendritic cells (immune cells) primed against HER3/HER2 proteins can boost the effectiveness of standard chemo in treating certain breast cancers.

How Is the Trial Designed?

Group I: Dendritic Cell Vaccine dose Escalation Experimental Treatment 2 Interventions

Dose escalation to determine the maximum tolerated dose (MTD) of HER2- and HER3- primed DC1 study vaccines. Participants will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A total of 3 dose levels will be used.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

The Shulas' Foundation

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

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 study identified nine specific HER3 peptides that can stimulate a strong CD4+ Th1 immune response, which is crucial for attacking tumors, in both healthy individuals and breast cancer patients.

Vaccination with HER3 peptide-pulsed dendritic cells not only prevented tumor development but also significantly delayed tumor growth and caused regression in various HER3-expressing tumor models, highlighting the potential of these peptides in immunotherapy for cancers overexpressing HER3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Immunogenic MHC Class II Human HER3 Peptides that Mediate Anti-HER3 CD4+ Th1 Responses and Potential Use as a Cancer Vaccine. Basu, A., Albert, GK., Awshah, S., et al.[2023]

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]

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]

HER2-specific T cells generated from dendritic cells modified with the HER2 gene effectively killed both trastuzumab-sensitive (SK-BR-3) and trastuzumab-resistant (MDA-MB-453) breast cancer cells, demonstrating a potential new immunotherapy approach for HER2-positive breast cancer.

The study found that these T cells had minimal cytotoxicity against HER2-negative breast cancer cell lines, indicating a targeted mechanism of action that could reduce side effects while effectively treating HER2-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro. Lin, XL., Wang, XL., Ma, B., 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]

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]

HER2 is a key target in breast cancer treatment, as it is over-expressed in 20-30% of cases, and therapies using HER2-directed monoclonal antibodies have significantly improved outcomes for patients with these tumors.

While early phase clinical trials have shown promise for HER2 vaccines, late phase trials have not yet produced clinically relevant results, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical development of vaccines for HER2+ breast cancer: Current landscape and future perspectives. Costa, RLB., Soliman, H., Czerniecki, BJ.[2017]

A HER-2-targeted dendritic cell vaccine has shown promise in eliminating HER-2-overexpressing cells in patients with high-risk ductal carcinoma in situ (DCIS), potentially reducing the risk of cancer recurrence.

Vaccination with this targeted approach may not only protect against the progression to invasive breast cancer but also reduce the side effects associated with traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of vaccines for high-risk ductal carcinoma in situ of the breast. Czerniecki, BJ., Roses, RE., Koski, GK.[2021]

Citations

1. moffitt.org moffitt.org/for-healthcare-professionals/clinical-perspectives/clinical-perspectives-story-archive/now-enrolling--novel-dendritic-cell-vaccines-immunotherapy-trial-for-her2-breast-cancer/

Novel Dendritic Cell Vaccines Immunotherapy Trial For ... Dendritic cell vaccines study offers hope for a less toxic, more personalized approach for the treatment of HER2 breast cancer with less chemotherapy and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3330145/

HER-2 Pulsed Dendritic Cell Vaccine Can Eliminate ... This clinical DC HER-2/neu vaccine was successful in inducing strong long-lasting immune responses (23) and either reducing or eliminating HER-2/neu expression ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10315441/

Efficacy of a Dual-Epitope Dendritic Cell Vaccine as Part of ... These data suggest that autologous DC vaccination when given with anti-HER2–directed mAb therapy and vinorelbine is safe and can induce immune responses, ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS629

and HER3-primed dendritic cells injections ... DecipHER is a dose-escalation, dose-expansion phase 1 trial designed to assess the safety and the preliminary efficacy of autologous, HER2- and HER3-primed DCs.

5. docwirenews.com docwirenews.com/post/using-dendritic-cell-vaccines-to-boost-neoadjuvant-therapy-in-her2-breast-cancer

Using Dendritic Cell Vaccines to Boost Neoadjuvant ... Pilot study shows HER2-targeted dendritic cell vaccines may enhance immune response in early HER2-positive breast cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02018458?tab=table

Safety Study Of Chemotherapy Combined With Dendritic ... Our goals are to boost T cell immunity targeted against breast cancer utilizing a tumor antigen-loaded DC vaccine, to enhance chemotherapy effectiveness and ...