Clinical Trials /

Standard of Care Chemotherapy Plus Pembrolizumab for Breast Cancer



The goal of this study is to establish the safety and tolerability of pembrolizumab when administered in combination with either of two chemotherapy regimens (weekly paclitaxel or capecitabine) in unresectable/metastatic triple negative breast cancer (MTNBC) patients.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting


Phase 1/Phase 2

Trial Eligibility



  • Brief Title: Standard of Care Chemotherapy Plus Pembrolizumab for Breast Cancer
  • Official Title: A Pilot and Phase II Study to Assess the Safety, Tolerability and Efficacy of Pembrolizumab Plus Chemotherapy in Metastatic Triple Negative Breast Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: 16-001
  • NCT ID: NCT02734290


  • Triple Negative Breast Cancer


PembrolizumabKeytrudaArm A
PaclitaxelTaxolArm A
CapecitabineXelodaArm B


The goal of this study is to establish the safety and tolerability of pembrolizumab when administered in combination with either of two chemotherapy regimens (weekly paclitaxel or capecitabine) in unresectable/metastatic triple negative breast cancer (MTNBC) patients.

Detailed Description

      In the pilot phase, patients will be enrolled to one of two experimental arms, which will be
      selected by the treating investigator (arm A: pembrolizumab + weekly paclitaxel; arm B:
      pembrolizumab + capecitabine).

      Subjects will receive pembrolizumab via intravenous (IV) infusion at 200mg every three weeks
      (Q3W), and continue treatment Q3W until progression of disease, initiation of alternative
      cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur, up to
      24 months.

      Paclitaxel will be administered intervenously on a weekly schedule at a dose of 80mg/m2.

      Oral capecitabine will be administered at total daily dose of 4,000 mg (2,000 mg two times
      each day (abbreviated BID)). Capecitabine will be administered as intermittent therapy given
      on days 1-7 in 14-day cycles.

Trial Arms

Arm AExperimentalpembrolizumab + weekly paclitaxel
  • Pembrolizumab
  • Paclitaxel
Arm BExperimentalpembrolizumab + capecitabine
  • Pembrolizumab
  • Capecitabine

Eligibility Criteria

        Inclusion Criteria:

        Be willing and able to provide written informed consent/assent for the trial.

          -  Be 18 years of age on day of signing informed consent.

          -  HER2-negative breast cancer (defined by immunohistochemistry (IHC) 0-1 (or) IHC 2 and
             in situ hybridization (ISH) HER2 / centromere on chromosome 17 (CEP17) < 2.0);

          -  ER and PR-negative breast cancer (defined by IHC<1%);

          -  Measurable metastatic or unresectable disease based on response evaluation criteria in
             solid tumours (RECIST) 1.1.

          -  Indicated for treatment with either weekly paclitaxel or oral capecitabine, as first
             or second-line chemotherapy in the metastatic/unresectable setting (as determined by
             the consenting investigator);

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained during screening.
             Archival tissue is acceptable if no intervening anti-neoplastic therapy has been
             administered, and if sufficient material is available for analysis (see section 8.0
             for requirements);

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrate adequate organ function as defined by protocol defined lab values

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential must avoid becoming pregnant while on
             treatment. Men must avoid fathering a child while on treatment.

        Exclusion Criteria:

          -  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 treatment.

          -  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 trial

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study,
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier. Denosumab is allowed.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent. Note: Subjects
             with ≤ Grade 2 neuropathy and alopecia are an exception to this criterion and may
             qualify for the study.

          -  Has received the assigned chemotherapy regimen previously in the metastatic setting,
             or has received the assigned chemotherapy regimen previously in the (neo)adjuvant
             setting within 12 months of consent;

          -  If subject received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.

          -  Has a known additional malignancy that progressed or required active treatment in the
             last 5 years.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

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

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

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

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

          -  Has received prior therapy with an anti-programmed death 1 (anti-PD-1),
             anti-programmed death ligand 1 (anti-PD-L1), or anti-programmed death ligand 2
             (anti-PD-L2) agent or has participated in a Merck-sponsored pembrolizumab study.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B or Hepatitis C.

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-Associated Adverse Events
Time Frame:6 weeks
Safety Issue:
Description:The count of serious adverse events and grade III/IV treatment-associated adverse events requiring discontinuation of pembrolizumab during that period.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:12 weeks
Safety Issue:
Description:Patients will have a computerized tomography (CT) scan (preferred) or magnetic resonance imaging (MRI) scan at 12 weeks to measure the size of target lesions. The percentage of patients whose tumors respond to treatment at 12 weeks will be compared to historical controls.


Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Providence Health & Services

Trial Keywords

  • metastatic
  • Human epidermal growth factor receptor 2 (HER2) negative breast cancer
  • Estrogen Receptor (ER) negative breast cancer
  • Progesterone Receptor (PR) negative breast cancer
  • Immunotherapy
  • Breast Cancer

Last Updated

October 29, 2019