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Phase II Study of Pembrolizumab and Nab-paclitaxel in HER-2 Negative Metastatic Breast Cancer

NCT02752685

Description:

This is a single-arm open-label multi-cohort Phase II study evaluating the safety/tolerability and clinical activity of the combination of nab-paclitaxel and the antibody against programmed cell death 1 (PD-1), pembrolizumab, in patients with human epidermal growth factor receptor (HER-2) negative metastatic breast cancer (n=50). There will be two cohorts of patients consisting of a triple negative breast cancer (TNBC) cohort with 30 subjects and a hormone receptor (HR)-positive cohort with 20 subjects. There will be an initial safety run-in with 12 subjects from the TNBC and HR-positive cohort (~ 6 patients from each cohort). If no unexpected toxicity is observed (as defined in the study protocol), then enrollment will continue to complete both cohorts (30 total TNBC, 20 total in HR positive cohort). The subjects from the run in safety part will be included in the Phase II analysis. Tumor expression of programmed cell death ligand 1 (PD-L1) is not required for enrollment in the study, but will be assessed as possible predictive marker.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Trial Eligibility

Document

Phase II Study of <span class="go-doc-concept go-doc-intervention">Pembrolizumab and Nab-paclitaxel</span> in <span class="go-doc-concept go-doc-biomarker">HER-2</span> Negative <span class="go-doc-concept go-doc-disease">Metastatic Breast Cancer</span>

Title

  • Brief Title: Phase II Study of Pembrolizumab and Nab-paclitaxel in HER-2 Negative Metastatic Breast Cancer
  • Official Title: Phase II Study of Pembrolizumab and Nab-paclitaxel in HER-2 Negative Metastatic Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02752685

    ORG ID: 15-00441

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Pembrolizumab MK-3475 Pembrolizumab and Nab-Paclitaxel
    Nab-Paclitaxel Abraxane Pembrolizumab and Nab-Paclitaxel

    Trial Purpose

    This is a single-arm open-label multi-cohort Phase II study evaluating the
    safety/tolerability and clinical activity of the combination of nab-paclitaxel and the
    antibody against programmed cell death 1 (PD-1), pembrolizumab, in patients with human
    epidermal growth factor receptor (HER-2) negative metastatic breast cancer (n=50). There
    will be two cohorts of patients consisting of a triple negative breast cancer (TNBC) cohort
    with 30 subjects and a hormone receptor (HR)-positive cohort with 20 subjects. There will be
    an initial safety run-in with 12 subjects from the TNBC and HR-positive cohort (~ 6 patients
    from each cohort). If no unexpected toxicity is observed (as defined in the study protocol),
    then enrollment will continue to complete both cohorts (30 total TNBC, 20 total in HR
    positive cohort). The subjects from the run in safety part will be included in the Phase II
    analysis. Tumor expression of programmed cell death ligand 1 (PD-L1) is not required for
    enrollment in the study, but will be assessed as possible predictive marker.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Pembrolizumab and Nab-Paclitaxel Experimental Pembrolizumab and Nab-Paclitaxel will be combined together in the following doses. Pemborlizumab - 200 mg (IV infusion) Day 1 of each 3 week cycle. Start with Cycle 2 only Nab-Paclitaxel 100 mg/m2 (IV infusion) Day 1 and 8 of each 3 week cycle Pembrolizumab, Nab-Paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    - Have histologically confirmed adenocarcinoma of the breast that is either TNBC or HR
    positive/HER-2 negative. TNBC is defined as: ER/PR <1% and HER-2 negative disease
    (IHC 0-1+ or 2+ with HER2/17 ratio on FISH 1.8) according to ASCO/CAP
    guidelines11,67. HR positive is defined as: ER/PR >= 1% and HER-2 negative as per
    ASCO/CAP guidelines.

    - Have received 0-2 lines of cytotoxic chemotherapy for metastatic breast cancer
    endocrine therapy and/or targeted therapy is allowed.

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

    - Be 18 years of age on day of signing informed consent. Have measurable disease based
    on RECIST 1.1.

    - 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 up to 6 weeks (42
    days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained
    samples cannot be provided (e.g. inaccessible or subject safety concern) may submit
    an archived specimen only upon agreement from the PI or designee.

    - Have a performance status of 0 or 1 on the ECOG Performance Scale. Be willing to
    undergo tissue biopsies as mandatory as per protocol for patients with biopsy
    accessible disease.

    - Must have </= Grade 1 pre-existing peripheral neuropathy (as per CTCAE).

    - Demonstrate adequate organ function as defined in all screening labs should be
    performed within 10 days of treatment initiation.

    - Female subject of childbearing potential should have a negative urine or serum
    pregnancy within 72 hours prior to receiving the first dose of study medication. This
    applies even if the subject practices true abstinence* from heterosexual contact. If
    the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
    will be required.

    - A female subject of childbearing potential is a sexually mature women who (1) has not
    undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy
    [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal
    for at least 24 consecutive months [i.e., has had menses at any time during the
    preceding 24 consecutive months]. The female subject must: either commit to true
    abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or
    agree to use, and be able to comply with, effective contraception without
    interruption (2 methods of birth control), 28 days prior to starting IP therapy
    (including dose interruptions), and while on study medication or for a longer period
    if required by local regulations following the last dose of IP.

    - Male subjects must practice true abstinence* or agree to use a condom during sexual
    contact with a pregnant female or female of childbearing potential starting with the
    first dose of study therapy, during dose interruptions, and for up to 6 months
    following last dose of study therapy, even if he has undergone a successful
    vasectomy.

    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 treatment.

    - 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.

    - Taxane therapy within the past 3 months (90 days) prior to study Day 1.

    - 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 are an exception to this criterion and
    may qualify for the study.

    - Note: 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 treatment within the
    last five years. Exceptions include basal cell carcinoma of the skin or squamous cell
    carcinoma of the skin that has undergone potentially curative therapy or in situ
    cervical cancer.

    - 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 known 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-PD-1, anti-PD-L1, or anti-PD-L2 agent.

    - Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies,
    testing not mandatory).

    - Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
    [qualitative] is detected).

    - Has received a live vaccine within 30 days of planned start of study therapy

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Best Overall Response Rate (BORR)

    Secondary Outcome Measures

    Progression Free Survival

    Overall Survival

    Trial Keywords

    Nab-Paclitaxel

    Abraxane

    MK-3475