You are being asked to take part in this study because you have inflammatory breast cancer
(IBC) or triple negative breast cancer (TNBC) that is metastatic (has spread to other parts
of the body).
The goal of this clinical research study is to learn if pembrolizumab (also called MK-3475
and Keytruda) can help to control metastatic IBC and TNBC. The safety of this drug will also
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive pembrolizumab by
vein over about 30 minutes on Day 1 (+/- 3 days) of each 21-day cycle.
On Day 1 of each cycle:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
At Cycles 3, every 3rd cycle after that (Cycles 6, 9, 12, and so on), and if the disease gets
worse, blood (about 10 tablespoons) will be drawn for biomarker and immune system testing.
About every 2 Cycles, you will have imaging scans to check the status of the disease as part
of standard of care.
Length of Study:
You may continue taking the study drug for up to 24 months, as long as the doctor thinks it
is in your best interest. You will no longer be able to take the study drug if the disease
gets worse, if intolerable side effects occur, or if you are unable to follow study
Your participation on the study will be over after the follow-up visits.
After you stop receiving the study drug:
- You will have a physical exam.
- Blood (about 10 tablespoons) will be drawn for routine tests.
- You will have the same imaging scans you had at screening to check the status of the
About 1 and 3 months after the last dose of study drug, you will be asked about your health
and any side effects you may have had. You may be asked during a routine clinic visit or you
may be called. If you are called, each call should last about 2 minutes.
This is an investigational study. Pembrolizumab is FDA approved and commercially available
for the treatment of metastatic melanoma. Its use in patients with metastatic IBC and TNBC is
investigational. The study doctor can describe how the study drug is designed to work.
Up to 35 participants will be enrolled in this study. All will take part in at MD Anderson.
1. Is willing and able to provide written informed consent for the trial.
2. Is a female or male and >/= 18 years of age
3. A).Has histological confirmation of HER2 normal breast carcinoma with a clinical
diagnosis of IBC based on presence of inflammatory changes in the involved breast,
including diffuse erythema and edema (peau d'orange), with or without an underlying
palpable mass involving the majority of the skin of the breast. Pathological evidence
of dermal lymphatic invasion should be noted but is not required for diagnosis of
inflammatory breast cancer regardless ER/PR status; OR B).Has histological
confirmation of triple negative breast carcinoma (HER2 normal, ER/PR < 10%) without
clinical diagnosis of IBC
4. Has stage IV or recurrent disease that has been treated
5. Has clinical response or stable disease for minimum of two months (three cycle of
every three week chemotherapy or 8 weeks of weekly regimen, etc.) after receiving any
prior chemotherapy for metastatic/recurrent disease. A minimum of two cycles (6-8
weeks) of chemotherapy is required to determine clinical response. Per RECIST criteria
1.1, Clinical response for measurable disease is defined as complete response (CR) or
partial response (PR); for non-measurable disease only (i.e. bone metastasis, ascites,
pleural effusion, and pathological lymph nodes >/= 10 to <15 mm short axis) is defined
as persistence of one or more non-target lesion(s) and no increase in overall tumor
6. Is HER2 normal, defined as HER2 0 or 1+ by IHC and negative by FISH if performed; or
HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not
7. Has a performance status of 0-1 on the ECOG Performance Scale.
8. Has adequate organ function as determined by the following laboratory values: ANC >/=
1,500 /mcL, Platelets >/=100,000 /mcL, Hgb >/= 9 g/dL, creatinine levels < 1.5 x ULN,
Total bilirubin </= 1.5 x ULN, ALT and AST </= 2.5 x ULN or </=5 x ULN for subjects
with liver metastases.
9. Subjects of childbearing potential should be willing to use effective methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through at least 4 months after the last dose of study drug.Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year. Effective methods of birth control include 1). Use
of hormonal birth control methods: pills, shots/injections, implants (placed under the
skin by a health care provider), or patches (placed on the skin); 2).Intrauterine
devices (IUDs); 3).Using 2 barrier methods (each partner must use 1 barrier method)
with a spermicide. Males must use the male condom (latex or other synthetic material)
with spermicide. Females must choose either a Diaphragm with spermicide, or Cervical
cap with spermicide, or a sponge (spermicide is already in the contraceptive sponge).
10. Has negative serum or urine pregnancy test for subjects of childbearing potential.
1. Is currently participating in a study of an investigational anti-cancer agent.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy.
3. Has not recovered from adverse events due to prior therapies, i.e. monoclonal
antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or
surgery.( Note: Subjects with ≤ Grade 2 neuropathy, alopecia and general disorders and
administration site conditions (per CTCAE version 4.0) are an exception to this
criterion and may qualify for the study.)
4. Has a known malignancy (other than breast cancer) except basal cell carcinoma or
squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone
potentially curative therapy.
5. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate if they
are stable, and have no evidence of new or enlarging brain metastases, and are not
using steroids for at least 7 days prior to trial treatment.
6. Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
resolved childhood asthma/atopy would be an exception to this rule. Subjects that
require intermittent use of bronchodilators or local steroid injections would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
Sjorgen's syndrome will not be excluded from the study.
7. Has a history of (non-infectious) pneumonitis that required steroids or current
8. Has an active infection requiring systemic therapy.
9. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
10. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways) within 3 months.
11. Has a known history of Human Immunodeficiency Virus (HIV).
12. Has a known active Hepatitis B or Hepatitis C
13. Have received a live vaccine within 30 days prior to the first dose of trial
14. Is receiving concurrent anti-cancer therapy for metastatic disease