A Randomized Phase II Study Of Eribulin Mesylate With or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer

Patients must have histologically or cytologically confirmed Stage IV invasive breast cancer. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.

Subjects must have at least one lesion that is not within a previously radiated field that is evaluable on computerized tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version 1.1. If the subject's only evaluable disease is within a previously radiated field, it must have demonstrated progression since the time of radiation.

Participants must have HR positive, HER2-negative breast cancer (ER\>1% and/or, PR\>1%, HER2-negative per ASCO CAP guidelines, 2013 resulted on the primary tumor and/or a metastatic lesion).

Participants must have already received or been intolerant to at least two lines of hormonal therapies (including the adjuvant or metastatic setting) or be appropriate candidates for chemotherapy

Prior chemotherapy: Participants are allowed to have received up to 2 prior lines of chemotherapy in the metastatic setting. If a prior chemotherapy was given for less than 1 cycle, it will not be counted as a prior line. The last dose of chemotherapy must be ≥14 days prior to initiation of study therapy. Participants should be adequately recovered from acute toxicities of prior treatment. No prior treatment with eribulin mesylate is allowed.

Prior biologic therapy: The last dose of biologic or investigational therapy must be ≥21 days prior to initiation of study therapy.

Prior hormonal therapy: Hormonal therapy must have been discontinued ≥14 days prior to initiation of study therapy. However, continuation of ovarian suppression is allowed.

Prior radiation therapy: Participants may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed ≥14 days prior to initiation of study therapy.

Prior targeted therapy: Targeted therapy must have been discontinued ≥ 14 days prior to initiation of study therapy.

Biphosphonates/Denosumab: Participants on bisphosphonates/denosumab may continue receiving bisphosphonate therapy during study treatment.

Participants must have an archival tumor sample available (1 block or 20 unstained slides). If no archival tissue is available, participants must be willing to undergo a research biopsy of their disease if it is safely accessible.

Age ≥ 18 years of age

ECOG performance status ≤2 (Karnofsky ≥60%)

Participants must have normal organ and marrow function as defined below:

absolute neutrophil count ≥1,500/mcL

platelets ≥100,000/mcL

hemoglobin ≥ 8 g/dl

total bilirubin ≤1.5 × institutional upper limit of normal (ULN)

AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (≤ 5 × institutional ULN with documented liver metastases,

serum creatinine ≤1.5mg/dL or calculated GFR ≥60 mL/min

INR/PT ≤1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants

aPTT/PTT ≤1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants

The effects of eribulin mesylate and pembrolizumab on the developing human fetus are unknown. Pre-clinical data was suggestive of a teratogenic effect of eribulin mesylate. For these reasons women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and 4 months after the last dose of eribulin mesylate and/or pembrolizumab. 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, the treating physician and principal investigator should be informed immediately.

* While on the study, women must not breastfeed.

* Subjects of childbearing potential are defined as those who have not been surgically sterilized and/or have had a menstrual period in the past year

Female subjects of childbearing potential, as defined above, must have a either a negative urine or a negative serum pregnancy test within seven (7) days of first dose of pembrolizumab. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Ability to understand and willingness to sign a written informed consent document.

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, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, severe malnutrition or psychiatric illness/social situations that would limit compliance with study requirements.

Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc (\[QT interval/corrected QT interval\], eg, a repeated demonstration of a QTc interval \>500 ms).

Medcial condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, participants with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

History or evidence of active, noninfectious pneumonitis that required treatment with steroids.

History of interstitial lung disease.

Participants known to be positive for the human immunodeficiency virus (HIV), Hepatitis B antigen (HepBsAg), or Hepatitis C virus (HCV) RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Pembrolizumab and/or eribulin mesylate. In addition, these participants are at increased risk of lethal infections.

Has received a live vaccine within 28 days of planned start of study therapy.

What this study is about