Study of Pembrolizumab (MK-3475) Monotherapy for Metastatic Triple-Negative Breast Cancer (MK-3475-086/KEYNOTE-086)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Pembrolizumab
Intervention description: IV infusion of 200 mg.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 254.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Summary:

      This is a two-part study of pembrolizumab monotherapy in participants with metastatic
      triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and
      safety of pembrolizumab monotherapy as first line or above treatment in participants who have
      received either no prior systemic treatment or at least one prior systemic treatment for
      metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of
      pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after
      enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.
    

Eligibility criteria:

        Inclusion Criteria:

        For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not
        count as a prior line of therapy.

        For second line plus monotherapy (Parts 1 and 2):

          -  Has received at least one systemic treatment for metastatic breast cancer

          -  Has documented disease progression on or after the most recent therapy

          -  Prior treatment must include an anthracycline and a taxane in the neoadjuvant,
             adjuvant, or metastatic setting

        For first line monotherapy (Part 1):

          -  Has received no prior systemic treatment for metastatic breast cancer

          -  Has PD-L1-positive mTNBC.

        For second line plus monotherapy (Part 2):

        - Has PD-L1 strong positive mTNBC

        For all parts:

          -  Has mTNBC confirmed by a central laboratory

          -  For biomarker analysis, adequate newly obtained core or excisional biopsy of a
             not-previously-irradiated metastatic tumor lesion (mandatory)

          -  Has measurable metastatic disease

          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Female participants of childbearing potential should be willing to use 2 methods of
             birth control or be surgically sterile, or abstain from heterosexual activity for the
             course of the study through 120 days after the last dose of study treatment

          -  Male participants should agree to use an adequate method of contraception starting
             with the first dose of study treatment through 120 days after the last dose of study
             treatment

          -  Has adequate organ function

        Exclusion Criteria:

          -  Is currently participating and receiving study treatment, or has participated in a
             study of an investigational agent and received study therapy or used an
             investigational device within 4 weeks prior to study Day 1

          -  Has received prior anti-cancer monoclonal antibody (mAb) therapy for direct
             anti-neoplastic treatment within 4 weeks prior to study Day 1

          -  Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within at least 2 weeks prior to study Day 1

          -  Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents
             administered within at least 2 weeks prior to study Day 1

          -  Has an active autoimmune disease requiring systemic treatment in past 2 years

          -  Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of study
             treatment

          -  Has known additional malignancy that progressed or required active treatment within
             the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell
             carcinoma of the skin that has undergone potentially curative therapy, or in situ
             cervical cancer

          -  Has radiographically-detectable central nervous system (CNS) metastases and/or
             carcinomatous meningitis

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis or a history of interstitial lung disease

          -  Has an active infection requiring systemic therapy

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the study

          -  Is pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment

          -  Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
             anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell
             receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137) or
             has participated in Merck MK-3475 (pembrolizumab) study

          -  Has a known history of human immunodeficiency virus (HIV)

          -  Has known active Hepatitis B or C

          -  Has received a live vaccine within 30 days of planned start of study treatment