Immunotherapy + Chemotherapy for Breast Cancer

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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a 2-cohort, open-label, multicenter, phase 2 study of a short course of immunotherapy consisting of sequential decitabine followed by pembrolizumab administered prior to a standard neoadjuvant chemotherapy regimen for patients with locally advanced HER2-negative breast cancer. The primary efficacy objective is to determine if the immunotherapy increases the presence and percentage of tumor and/or stromal area of infiltrating lymphocytes prior to initiation of standard neoadjuvant chemotherapy. At enrollment, patients will be assigned to one of 2 cohorts based on hormone receptor status. * Cohort A - patients with HER2-negative, hormone receptor-negative breast cancer (defined as both ER and PgR with \< 10% positive staining on IHC) Note: before beginning standard neoadjuvant chemotherapy, patients in Cohort A may be reassigned to Cohort A2 to receive extended pembrolizumab as part of new standard neoadjuvant and postoperative adjuvant therapy. * Cohort B - patients with HER2-negative, hormone receptor-positive breast cancer (defined as either ER or PgR with ≥ 10% positive staining on IHC)

Research Team

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

Principal Investigator

Massey Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+