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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

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

  • ORG STUDY ID: 15-00441
  • NCT ID: NCT02752685

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabMK-3475hormone receptor (HR)-positive cohort
Nab-PaclitaxelAbraxanehormone receptor (HR)-positive cohort

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.

Trial Arms

NameTypeDescriptionInterventions
triple negative breast cancer (TNBC)
  • Pembrolizumab
  • Nab-Paclitaxel
hormone receptor (HR)-positive cohort(currently not recruiting for this group)
  • 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best Overall Response Rate (BORR)
Time Frame:Baseline through 2 years
Safety Issue:
Description:This is measured by RECIST version 1.1* (As published in the European Journal of Cancer:) will be used in this study for assessment of tumor response.

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:Baseline through 2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Baseline up through 2 years
Safety Issue:
Description:

Details

Phase:
Primary Purpose:Observational
Overall Status:Recruiting
Lead Sponsor:NYU Langone Health

Trial Keywords

  • Nab-Paclitaxel
  • Abraxane
  • MK-3475

Last Updated

October 23, 2020