Eribulin Mesylate with or without Pembrolizumab in Treating Patients with Hormone Receptor Positive and HER2 Negative Stage IV Breast Cancer

Inclusion Criteria

• 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 (estrogen receptor [ER] > 1% and/or, progesterone receptor [PR] > 1%, HER2-negative per American Society of Clinical Oncology [ASCO] College of American Pathologists [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
• 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
• The last dose of biologic or investigational therapy must be >= 21 days prior to initiation of study therapy
• Hormonal therapy must have been discontinued >= 14 days prior to initiation of study therapy; however, continuation of ovarian suppression is allowed
• Participants may have received prior radiation therapy in either the metastatic or early-stage setting; radiation therapy must be completed at least >= 14 days prior to initiation of study therapy
• Targeted therapy must have been discontinued >= 14 days prior to initiation of study therapy
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dl
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN) (=< 5.0 x institutional ULN with documented liver metastases)
• Serum creatinine =< 1.5 mg/dL or calculated glomerular filtration rate (GFR) >= 60 mL/min
• International normalized ratio (INR)/prothrombin time (PT) =< 1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated PTT (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
• 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 must have 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
• INCLUSION CRITERIA FOR CROSSOVER THERAPY
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 75,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (=< 1.5 x institutional upper limit of normal [ULN] in patients with well documented Gilbert’s syndrome)
• AST/(SGOT)/ALT(SGPT) =< 3.0 x institutional upper limit of normal (ULN) (=< 5.0 x institutional ULN with documented liver metastases)
• Female subjects of childbearing potential, must have 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
• Participants with accessible disease must be willing to undergo a research biopsy before beginning crossover therapy

Exclusion Criteria

• Chemotherapy-related or radiation-related toxicities that have not resolved to grade 1 severity or lower, except for stable sensory neuropathy (=< grade 2) and alopecia
• Participants who are receiving any other investigational agents
• Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2 agent or participation in any MK-3475 Merck studies
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin mesylate or pembrolizumab
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 4 weeks prior to registration, are neurologically stable and absence of new neurologic symptoms for the last 4 weeks prior to study entry, and have recovered from the effects of radiotherapy or surgery; any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= 2 weeks before the first study drug; treatment for brain metastases may have included whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician
• 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], e.g., a repeated demonstration of a QTc interval > 500 ms)
• Medical 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 (e.g., 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) ribonucleic acid (RNA); HIV-positive participants on combination antiretroviral therapy are ineligible
• 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; patients 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
• Has received a live vaccine within 28 days of planned start of study therapy
• EXCLUSION CRITERIA FOR CROSSOVER THERAPY: Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)
• EXCLUSION CRITERIA FOR CROSSOVER THERAPY: History or evidence of active, noninfectious pneumonitis that required treatment with steroids