Clinical Trials /

Safety and Efficacy Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy as Neoadjuvant Treatment for Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-173/KEYNOTE 173)

NCT02622074

Description:

The purpose of this study is to evaluate the safety, tolerability and clinical activity of pembrolizumab (MK-3475) in combination with six chemotherapy regimens as neoadjuvant treatment for participants with triple negative breast cancer (TNBC). The primary objectives of this study are: 1) to determine the safety and tolerability and 2) to establish a recommended Phase 2 dose for the six combination regimens as a neoadjuvant treatments for participants with TNBC.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Safety and Efficacy Study of <span class="go-doc-concept go-doc-intervention">Pembrolizumab (MK-3475)</span> in Combination With <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> as Neoadjuvant Treatment for Participants With <span class="go-doc-concept go-doc-alteration">Triple Negative Breast Cancer</span> (<span class="go-doc-concept go-doc-alteration">TNBC</span>) (<span class="go-doc-concept go-doc-intervention">MK-3475</span>-173/KEYNOTE 173)

Title

  • Brief Title: Safety and Efficacy Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy as Neoadjuvant Treatment for Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-173/KEYNOTE 173)
  • Official Title: A Phase 1b Study to Evaluate Safety and Clinical Activity of Pembrolizumab (MK-3475) in Combination With Chemotherapy as Neoadjuvant Treatment for Triple Negative Breast Cancer (TNBC) - (KEYNOTE 173)
  • Clinical Trial IDs

    NCT ID: NCT02622074

    ORG ID: 3475-173

    NCI ID: 2015-002405-11

    Trial Conditions

    Triple Negative Breast Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    Nab-paclitaxel Pembro+NpPembro+A+C, Pembro+Np+CbPembro+A+C
    Anthracycline Pembro+NpPembro+A+C, Pembro+Np+CbPembro+A+C
    Cyclophosphamide Pembro+NpPembro+A+C, Pembro+Np+CbPembro+A+C
    Carboplatin Pembro+Np+CbPembro+A+C

    Trial Purpose

    The purpose of this study is to evaluate the safety, tolerability and clinical activity of
    pembrolizumab (MK-3475) in combination with two chemotherapy regimens as neoadjuvant
    treatment for participants with triple negative breast cancer (TNBC).

    The primary objectives of this study are: 1) to determine the safety and tolerability and 2)
    to establish a recommended Phase 2 dose for the two combination regimens: 1) pembrolizumab +
    nab-paclitaxel followed by pembrolizumab + doxorubicin + cyclophosphamide; and 2)
    pembrolizumab + nab-paclitaxel + carboplatin followed by pembrolizumab + doxorubicin +
    cyclophosphamide, as a neoadjuvant treatments for participants with TNBC.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Pembro+NpPembro+A+C Experimental Participants receive pembrolizumab (pembro) intravenously (IV) PLUS nab-paclitaxel (Np) IV; followed by pembrolizumab IV PLUS anthracycline (e.g. doxorubicin) (A) IV PLUS cyclophosphamide (C) IV. Nab-paclitaxel, Anthracycline, Cyclophosphamide
    Pembro+Np+CbPembro+A+C Experimental Participants receive pembrolizumab (pembro) IV PLUS nab-paclitaxel (Np) IV PLUS carboplatin (Cb) IV; followed by pembrolizumab IV PLUS anthracycline (e.g. doxorubicin) (A) IV PLUS cyclophosphamide (C) IV. Nab-paclitaxel, Anthracycline, Cyclophosphamide, Carboplatin

    Eligibility Criteria

    Inclusion Criteria:

    - Has previously untreated, locally advanced TNBC.

    - Is able to provide 2 core needle biopsies from the primary tumor at screening to the
    central laboratory and agrees to have a core needle biopsy after single dose
    pembrolizumab treatment if tumor biopsy is feasible as judged by the investigator.

    - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    - Has adequate organ function.

    - Females of childbearing potential must be willing to use adequate contraception for
    the course of the study through 12 months after the last dose of study drug for
    participants receiving cyclophosphamide and through 6 months after the last dose of
    study drug for participants who do not receive cyclophosphamide.

    Exclusion Criteria:

    - Has evidence of metastatic breast cancer, concurrent bilateral invasive breast
    cancer, or inflammatory breast cancer.

    - Has another malignancy within the last 5 years. Exceptions include basal cell
    carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
    potentially curative surgery, or in situ cervical cancer.

    - Has received prior chemotherapy, targeted therapy, radiation therapy, immunotherapy
    that targets immune checkpoints, co-stimulatory or co-inhibitory pathways for T cell
    receptors within the past 12 months.

    - Is currently participating and receiving study therapy, or has participated in a
    study of an investigational agent and received study therapy or used an
    investigational device within 4 weeks of the first dose of study drug.

    - Has received a live vaccine within 30 days of the first dose of study drug.

    - Has an active autoimmune disease that has required systemic treatment in past 2
    years.

    - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
    other form of immunosuppressive therapy within 7 days prior to the first dose of
    study drug.

    - Has a known history of Human Immunodeficiency Virus (HIV).

    - Has known active Hepatitis B or Hepatitis C.

    - Has evidence of active, non-infectious pneumonitis.

    - Has history of pneumonitis requiring treatment with steroids or history of
    interstitial lung disease.

    - Has an active infection requiring systemic therapy.

    - Has significant cardiovascular disease, such as: History of myocardial infarction,
    acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the
    last 6 months; Congestive heart failure (CHF) New York Heart Association (NYHA) Class
    II-IV or history of CHF NYHA class III or IV

    - Has known psychiatric or substance abuse disorders that would interfere with
    cooperation with the requirements of the study.

    - Is pregnant or breastfeeding, or expecting to conceive children within the projected
    duration of the study, starting with the screening visit through 120 days after the
    last dose of study drug.

    - Has a known hypersensitivity to the components of the study drug or its analogs.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Number of Participants with Dose Limiting Toxicities

    Secondary Outcome Measures

    Number of Participants with a Pathological Complete Response

    Trial Keywords

    PD1

    PD-1

    PDL1

    PD-L1

    Triple Negative Breast Cancer