Immunotherapy + Chemotherapy for Breast Cancer

Not currently recruiting at 4 trial locations

Overseen By Massey SIIT Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Metastatic disease, Cardiac disease, Autoimmune, 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)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with HER2-negative breast cancer. It aims to determine if adding immunotherapy (using pembrolizumab) before chemotherapy can enhance the body's ability to fight the cancer. The focus is on increasing immune cells in the tumor area to boost chemotherapy effectiveness. The trial includes different treatment plans based on whether the cancer is hormone receptor-positive or negative. Those diagnosed with locally advanced HER2-negative breast cancer who have not yet started treatment might be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these, as they are generally not allowed within 7 days prior to starting the study treatment, unless they are equivalent to or less than an oral prednisone dose of 10 mg daily.

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

Research has shown that combining decitabine and pembrolizumab holds promise for treating breast cancer. In a study on Triple Negative Breast Cancer (TNBC), 40.7% of patients experienced a complete response, meaning their cancer was no longer detectable. This suggests the treatment works for some individuals.

Adding pembrolizumab to chemotherapy has helped patients with advanced cancer live longer, indicating the treatment might be well-tolerated.

For HER2-negative, hormone receptor-positive breast cancer, the combination of decitabine and pembrolizumab is under study, but detailed safety results remain unclear. However, pembrolizumab has been safely combined with chemotherapy in other studies, usually with manageable side effects.

It is important to note that this study is still in the early stages. These treatments have shown some success in other contexts, but more information is needed to fully understand their safety for this specific use. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care for breast cancer, which often involves chemotherapy and hormone therapies, the treatments in this trial are unique because they incorporate immunotherapy, specifically pembrolizumab, alongside chemotherapy. Researchers are particularly excited about pembrolizumab because it works by unleashing the immune system to target and destroy cancer cells, which is a different mechanism compared to traditional treatments that directly kill cancer cells. Additionally, for patients with Triple Negative Breast Cancer, the inclusion of decitabine, a drug that can modify DNA and potentially make tumors more susceptible to immune attacks, is a promising approach. These innovative combinations could offer new hope for patients who have limited options with existing therapies.

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

Research has shown that using decitabine with pembrolizumab can help the immune system combat triple-negative breast cancer (TNBC). In this trial, participants in Cohort A and Cohort A2 will receive this combination. One study found that this combination made the cancer undetectable in 40.7% of patients. Participants in Cohort A2 will also receive pembrolizumab with chemotherapy, which has been shown to reduce cancer growth or spread by 35% in TNBC patients. For HER2-negative hormone receptor-positive breast cancer, participants in Cohort B will receive pembrolizumab with chemotherapy, which has proven effective, with many patients responding well. These treatments suggest potential for enhancing the body's ability to fight these types of breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Harry D. Bear, M.D., Ph.D.

Principal Investigator

Massey Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with locally advanced HER2-negative breast cancer, either hormone receptor-positive or negative. Participants must not be pregnant, agree to contraception, and have proper liver, kidney, and bone marrow function. Exclusions include recent live vaccines, certain heart diseases, immunodeficiencies like HIV, active hepatitis B or C infections, prior treatments for current breast cancer diagnosis or other cancers within the last five years.

Inclusion Criteria

I am a woman who is not postmenopausal or without a hysterectomy and have a recent negative pregnancy test.

My breast cancer is either hormone receptor-positive or negative.

My breast cancer is at an advanced stage but has not spread to distant parts of my body.

Exclusion Criteria

I have been diagnosed with an immunodeficiency, such as HIV.

I have a moderate to severe nervous system disorder.

I haven't taken steroids or immunosuppressants in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immunotherapy

Participants receive decitabine followed by pembrolizumab to increase lymphocyte infiltration into tumor and/or stroma

4 weeks

Multiple visits for IV administration

Neoadjuvant Chemotherapy

Participants receive 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel or Nab-paclitaxel

16 weeks

Weekly visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of adverse events and response rates

12 months

Regular follow-up visits, including a 12-month evaluation

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cyclophosphamide
• Decitabine
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests if a short course of decitabine followed by pembrolizumab before standard chemo increases immune cells in tumors in patients with advanced HER2-negative breast cancer. It's divided into two groups based on hormone receptor status: one potentially receiving extended pembrolizumab treatment.

How Is the Trial Designed?

Group I: Cohort B: HER2-negative hormone receptor-positive tumors Experimental Treatment 5 Interventions

HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel.

Group II: Cohort A: Triple Negative Breast Cancer (TNBC) Experimental Treatment 6 Interventions

Triple Negative Breast Cancer (Cohort A): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin.

Group III: Cohort A2: Triple Negative Breast Cancer (TNBC) with Extended Pembrolizumab Experimental Treatment 6 Interventions

Triple Negative Breast Cancer (Cohort A2). Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four cycles of dose-dense doxorubicin and cyclophosphamide (AC), followed by 12 doses of weekly paclitaxel and carboplatin, and pembrolizumab every 3 weeks.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02957968?cond=%22Estrogen-Receptor%20Negative%20Breast%20Cancer%22&intr=%22Antirheumatic%20Agents%22&viewType=Table&rank=6&tab=results

Study Results | Neoadjuvant Pembrolizumab + Decitabine ... HER2-negative hormone receptor-positive tumors (Cohort B): Decitabine IV over 60 minutes on 4 days and pembrolizumab IV over 30 minutes on days 8 and 22. Four ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40021215/

a phase 2 neoadjuvant window trial of decitabine ... - PubMed We have shown that the DNMTi decitabine augments the effectiveness of immunotherapy using murine triple-negative breast cancer (TNBC) models.

3. nature.com nature.com/articles/s41523-024-00704-9

Immunotherapy for hormone receptor‒positive HER2- ... The predictive probability of success with pembrolizumab plus chemotherapy was >99%, thereby meeting the prespecified efficacy threshold. The ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825001568

Immunotherapy in primary hormone-receptor positive ... HR+ /HER2- BC patients achieved a pCR rate of 28 % vs 14 % of the control, however the benefit was attributed selectively to the highly proliferative, ER low ...

5. jitc.bmj.com jitc.bmj.com/content/13/2/e010294.info

T-cell immune checkpoint inhibition plus hypomethylation ... In this trial, we recruited patients with locally advanced HER2-negative breast cancer to explore the efficacy of using decitabine, a DNMTi, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9454514/

Phase II Study Combining Pembrolizumab with Aromatase ... The immune checkpoint inhibitor (ICI) pembrolizumab in combination with chemotherapy has shown significant progression-free survival (PFS) ...

7. clinicaltrial.be clinicaltrial.be/en/details/9610?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Neoadjuvant Pembrolizumab + Decitabine Followed by Std ... To determine and quantify if treatment with neoadjuvant decitabine followed by pembrolizumab increases lymphocyte infiltration into tumor and/or stroma in ...