Combination Therapy for Breast Cancer

Overseen By Rima Patel, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rima Patel

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: Metastases, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with locally advanced triple-negative breast cancer (TNBC), a type of breast cancer that does not respond to common hormonal therapies. Researchers aim to assess the safety of using dupilumab and pembrolizumab (two immune-boosting drugs) in combination with the chemotherapy drugs paclitaxel and carboplatin. Participants should have untreated TNBC with either a large tumor or cancer in nearby lymph nodes. The primary focus is on identifying any serious immune-related side effects. As a Phase 1 trial, this research seeks to understand 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 be on systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial, unless it's a stable low dose. It's best to discuss your specific medications with the trial team.

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

Previous studies have generally shown that dupilumab is well-tolerated. It has been tested for conditions like asthma and skin diseases, demonstrating a good safety record with mostly mild to moderate side effects. Some patients reported skin reactions, but serious problems were rare.

Research has shown that pembrolizumab, when combined with chemotherapy, has been safely used to treat triple-negative breast cancer and is associated with longer survival rates. However, some patients experienced immune-related side effects, which were usually manageable.

As this is an early-phase trial, the main goal is to assess the safety of using these drugs together. While both drugs have shown safety individually, this combination is new, so monitoring for side effects is crucial. Participants in this trial may help doctors determine the safety of this treatment for future patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Dupilumab and Pembrolizumab for advanced triple negative breast cancer (TNBC) because it offers a novel approach compared to the current standard treatments, which typically include chemotherapy and single-agent immunotherapies. Dupilumab, primarily known for treating conditions like eczema and asthma, targets the IL-4 and IL-13 pathways, potentially modulating the immune environment differently than existing cancer therapies. Pembrolizumab, a well-known checkpoint inhibitor, boosts the immune system's ability to fight cancer by targeting the PD-1/PD-L1 pathway. The combination of these two drugs could provide a complementary attack on cancer cells, potentially leading to better responses in patients who have limited options.

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

Research has shown that adding pembrolizumab to chemotherapy can extend the lives of patients with advanced triple-negative breast cancer (TNBC). Studies have found that using pembrolizumab before surgery can make the cancer completely disappear from tissue samples, indicating a positive outlook for longer survival. In this trial, some participants will receive pembrolizumab as part of their treatment.

Dupilumab is primarily used to treat eczema and asthma. Although limited information exists about its use in breast cancer, it is believed to block certain signals in the immune system that aid cancer growth. This trial will explore the potential of combining these treatments, aiming to enhance the body's ability to fight cancer by boosting the immune response. ^{3 5 6 7 8}

Who Is on the Research Team?

Rima Patel, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Joseph Sparano, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for individuals with locally advanced triple negative breast cancer. Participants should be suitable for neoadjuvant therapy, which is treatment given before the main treatment to shrink a tumor.

Inclusion Criteria

My breast cancer is triple negative according to the latest guidelines.

Patients must be willing and able to have core needle biopsies of tumor prior to initiation of treatment

Patients must be willing and able to provide blood samples at specified time points

Exclusion Criteria

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

History of allergic reactions to specified compounds

History of transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive dupilumab, pembrolizumab, paclitaxel, and carboplatin

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab
• Pembrolizumab

Trial Overview The trial tests dupilumab (an IL-4 receptor antagonist) combined with pembrolizumab, paclitaxel, and carboplatin. It aims to assess safety and how well this combination works as an initial step in shrinking tumors before surgery.

How Is the Trial Designed?

Group I: Patients with locally advanced TNBC Experimental Treatment 4 Interventions

Patients with advanced triple negative breast cancer (TNBC).

Who Is Running the Clinical Trial?

Rima Patel

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Dupilumab (Dupixent) has been associated with a risk of ocular adverse reactions, highlighting the importance of monitoring patients for eye-related side effects during treatment.

Prompt management of any ocular issues is essential for patients receiving dupilumab, ensuring their safety and well-being while benefiting from the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., 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 review of 22 studies involving 3303 patients, dupilumab demonstrated significant efficacy in treating atopic dermatitis, with 85.1% of patients achieving at least a 50% improvement in their Eczema Area and Severity Index (EASI) score after 16 weeks of treatment.

While dupilumab is generally well-tolerated, conjunctivitis was the most common side effect, occurring in 26.1% of patients, highlighting the need for ongoing monitoring of adverse events in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis. Halling, AS., Loft, N., Silverberg, JI., et al.[2021]

Dupilumab is an effective treatment for type 2 inflammatory diseases like atopic dermatitis, asthma, and nasosinusal polyposis, as it inhibits the IL-4 receptor, blocking the action of key cytokines involved in these conditions.

The drug has a favorable safety profile, with few and reversible side effects, making it a promising option for patients who do not respond well to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. Russo, G., Laffitte, E.[2023]

Dupilumab is the first biological medication approved for treating moderate-to-severe atopic dermatitis, demonstrating significant effectiveness and a favorable safety profile.

Despite its overall safety, there have been rare cases of local Staphylococcus aureus infections reported in patients undergoing dupilumab treatment for atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Dupilumab leads to an increased chance of head and neck Staphylococcus aureus infection in atopic dermatitis patients. Chen, M., Gao, K., Ali, K., et al.[2023]

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Dupilumab effectively treats moderate-to-severe atopic dermatitis by blocking IL-4/IL-13 signaling, leading to significant improvements in clinical measures like SCORAD and EASI, as well as patient-reported outcomes such as itch severity.

The safety profile of dupilumab is better than traditional immunosuppressive drugs, with fewer skin infections reported compared to placebo, although it can cause injection-site reactions and conjunctivitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab for treatment of atopic dermatitis. Seegräber, M., Srour, J., Walter, A., et al.[2019]

Pembrolizumab has shown promising clinical activity in treating MSI-H/dMMR metastatic colorectal cancer, with a response rate of 45% and a median progression-free survival of 16.5 months, indicating its potential effectiveness.

The KEYSTEP-008 trial aims to explore whether combining pembrolizumab with other immune receptor targets can enhance its efficacy compared to using pembrolizumab alone, potentially leading to better outcomes for patients with chemotherapy-refractory or untreated MSI-H/dMMR mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYSTEP-008: phase II trial of pembrolizumab-based combination in MSI-H/dMMR metastatic colorectal cancer. André, T., Pietrantonio, F., Avallone, A., et al.[2023]

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