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.
- 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
- 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.
- 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.
- 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
- 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
- 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