| Eligibility |
Inclusion Criteria:
- Histologically proven, PDL1 (=1%) positive and/or tumor infiltrating lymphocytes
(TILs) positive (=1%), locally advanced "chest wall" breast cancer (with or without
distant metastases), who have been treated with chemotherapy or radiation therapy may
be eligible for this study. Patients with cutaneous metastases only (with or without
evidence of primary tumor) are also eligible;
- Patients must have tissue accessible for serial biopsies;
- Expected survival of > 3 months;
- Be willing and able to provide written informed consent/assent for the trial. The
subject may also provide consent/assent for Future Biomedical Research. However, the
subject may participate in the main trial without participating in Future Biomedical
Research. 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 Sponsor;
- Be 18 years of age on day of signing informed consent;
- Be a female or male subject with IBC with lymphangitic spread to the chest wall. ER,
PgR and HER2 status determination is required for enrollment;
- Have provided tissue for PD-L1 biomarker analysis from a newly obtained core or
excisional biopsy of a tumor lesion (mandatory) and received permission for enrollment
from the Core Lab based on the adequacy of the biopsy specimen. Repeat samples may be
required if adequate tissue is not provided;
- Have measurable metastatic disease based on irRECIST criteria as determined by central
radiology review. Tumor lesions situated in a previously irradiated area are
considered measurable, if progression has been demonstrated in such lesions. Note: The
exact same image acquisition and processing parameters should be used throughout the
study;
- Have a performance status of 0 or 1 on the ECOG Performance Scale. Assessment should
be performed within 10 days of treatment initiation;
- Female subjects of childbearing potential (Section 2.9.2) must be willing to use an
adequate method of contraception as outlined in Section 2.9.2 - Contraception, for the
course of the study through 120 days after the last dose of study medication;
- Male subjects childbearing potential (Section 2.9.2) must agree to use an adequate
method of contraception as outlined in Section 2.9.2- Contraception, starting with the
first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject;
- Female subjects of childbearing potential should have a negative urine or serum
pregnancy test 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;
- Patients with hormone receptor-positive and/or HER2-positive breast cancer would be
eligible for the study only if their disease is considered refractory to hormonal or
anti-HER2 agents, respectively, and no further hormonal or anti-HER2 treatment is
indicated;
- Demonstrate adequate organ function as defined in protocol, 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. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required;
- Female subjects of childbearing potential (Section 5.7.2) must be willing to use an
adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the
course of the study through 120 days after the last dose of study medication. Note:
Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject;
- Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate
method of contraception as outlined in Section 5.7.1- Contraception, starting with the
first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
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;
- 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 1: Subjects
with = Grade 2 neuropathy are an exception to this criterion and may qualify for the
study. Note 2: 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 is progressing or requires active treatment.
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, or any evidence of active, non-infectious pneumonitis;
- 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);
- 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. 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.
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