This research study is a Pilot Study, which is the first time investigators are examining
this study intervention.
In this research study, the investigators are looking at how the participants body and tumor
respond to the combination of Nab-paclitaxel and Pembrolizumab. Also, the investigators will
be examining the participants tumor tissue to learn more about the disease.
The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for this
specific disease; but it has been approved in the United States for the treatment of other
The FDA has not approved Nab-paclitaxel as a treatment option for this type of breast cancer;
but it has been approved in the United States for the treatment of metastatic breast cancer
(breast cancer that has spread to other parts of the body).
Pembrolizumab is a medicine that may treat cancer by working with the participant's immune
system. The immune system is the body's natural defense against disease. The immune system
sends types of cells called "T cells" throughout the body to detect and fight infections and
diseases, including cancer. For some types of cancer, the T cells do not work as they should
and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a
protein in the T cells called PD-1 ("programmed death 1"), which then allows these cells and
other parts of the immune system to attack tumors.
Nab-paclitaxel (Abraxane) is part of a class of medications called antimicrotubule agents. It
works by stopping the growth and spread of cancer cells by blocking the action of proteins
The combination of Pembrolizumab and Nab-paclitaxel is investigational. "Investigational"
means that the combination of study drugs is being studied. The study drugs, when given
separately, work in different ways to stop the cancer cells from growing and spreading.
However, it is not known if giving the two study drugs at the same time will have a better
anti-cancer effect than giving each treatment on its own.
- Participants must have histologically or cytologically confirmed invasive breast
- Participants must have operable breast cancer, with tumors greater than or equal to 2
cm in size; Participants must not have any evidence of distant metastatic disease.
Inflammatory breast cancer is permitted.
- All confirmed invasive disease must have been tested for ER, PR, and HER2 and
participants must have hormone receptor-positive, HER2-negative breast cancer (ER>1%
or PR>1%, AND HER2-negative per ASCO CAP guidelines, 2013).
- Participants with multicentric, multifocal, and/or contralateral cancers are allowed
as long as one lesion meets eligibility and no biopsied tumor is HER2+.
- Prior systemic therapy: No prior chemotherapy, biologic therapy, hormonal therapy or
investigational therapy for this operable breast cancer.
- Prior radiation therapy: No prior radiation to the ipsilateral breast.
- The participant is ≥18 years old
- The participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤1
(see Appendix A)
- Participants must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥1500/mm3
- Platelets ≥100,000/mm3
- Hemoglobin ≥9 g/dL
- Total Bilirubin ≤1.5 mg/dL (< 2.0 in participants with known Gilbert's syndrome)
- Serum creatinine ≤1.5 mg/dL OR calculated GFR ≥60mL/min
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times
the upper limit of normal.
- International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the
upper limit of normal unless subject is receiving anticoagulant therapy, as long
as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Activated Partial Thromboplastin Time (aPTT) <1.5 times the upper limit of normal
unless subject is receiving anticoagulant therapy, as long as PT or PTT is within
therapeutic range of intended use of anticoagulants.
- The participant is capable of understanding and complying with the protocol and has
signed the informed consent document.
- The participant must be willing to undergo the three required research biopsies over
the course of protocol therapy. Participants who undergo an attempted research biopsy
procedure for the purpose of this protocol, and in whom inadequate tissue is obtained,
are not required to undergo a repeat biopsy in order to continue on protocol.
- The effects of pembrolizumab on the developing human fetus are unknown. For this
reason, both women and men of child-bearing potential must agree to use adequate
contraception (Section 5.5.2) starting with the first dose of study therapy and for
the duration of study participation, through 120 days after the last dose of study
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject. Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately. While on the study, women may not breast-feed. Women of childbearing potential
are defined as those who have not been surgically sterilized or have not been free from
menses for > 1 year.
- Female subject 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.
- Participants on bisphosphonates may continue receiving bisphosphonate therapy during
- The participant has received prior pembrolizumab or any other anti-PD-1, anti-PD-L1,
or anti-PD-L2 therapy, or has participated in any prior studies involving
- Hypersensitivity to pembrolizumab or any of its excipients.
- The participant has any history or evidence of active, non-infectious pneumonitis or
interstitial lung disease.
- The participant has an uncontrolled intercurrent illness including, but not limited
to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac
arrhythmia, congestive heart failure (New York Heart Association Class III or IV; see
Appendix B), active ischemic heart disease, myocardial infarction within the previous
six months, uncontrolled diabetes mellitus, chronic liver or renal disease, or severe
- Concurrent use of potent CYP3A4 inhibitors (see Appendix C), such as ketoconazole and
erythromycin, should be avoided during the study treatment with nab-paclitaxel.
- Pregnant women are excluded from this study because pembrolizumab has the potential
for teratogenic or abortifacient effects. Because there is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
pembrolizumab, breastfeeding should be discontinued if the mother is treated with
- Active infection requiring intravenous antibiotics at week 1 day 1.
- Individuals with a history of a second malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 5 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer
in situ, and non-melanoma cancer of the skin. Participants with other cancers
diagnosed within the past 5 years and felt to be at low risk of recurrence should be
discussed with the study sponsor to determine eligibility.
- The participant has a medical condition that requires chronic systemic steroid therapy
or any other form of immunosuppressive medication including disease modifying agents,
or has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
- The participant has an active autoimmune disease or a documented history of autoimmune
disease or syndrome that requires systemic steroids or immunosuppressive agents.
- The participant is known to be positive for Hepatitis B surface antigen, or Hepatitis
C RNA. Testing for screening is not required.
- Known HIV-positive participants.HIV-positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
pembrolizumab. In addition, these participants are at increased risk of lethal
infections with bone marrow suppressive therapy, i.e. nab-paclitaxel. Appropriate
studies will be undertaken in participants receiving combination antiretroviral
therapy when indicated. Testing for screening is not required.
- The participant has received a live vaccine within 28 days of planned start of study
- Seasonal influenza vaccines for infection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (i.e. Flu-Mist ®) are live
attenuated vaccines, and are not allowed.