A Phase 2 Study of Palliative Radiation in Combination with Pembrolizumab in Subjects with Unresectable Metastatic Stage IV Breast Cancer: Twisted Pink

Inclusion Criteria: * 1\. Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures. 2\. Female age ≥ 18 years at the time of informed consent. 3. Histologically confirmed diagnosis of breast cancer. 4. Disease stage: unresectable or metastatic stage IV breast cancer. 5. Candidate for palliative SBRT independent from study enrollment 6. Measurable disease, defined as at least 1 visceral or nodal/soft tissue breast cancer lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by Computer Tomography scan or Magnetic Resonance Imaging. Lymph nodes must measure ≥ 15 mm in their short axis to be considered measurable by Computer Tomography scan or Magnetic Resonance Imaging or Positron Emission Tomography-CT. 7\. If subject received major surgery, must have recovered adequately from toxicity and/or complications from the intervention prior to enrollment. 8\. Subject must have received two prior lines of therapy and include a taxane in the adjuvant/neoadjuvant or metastatic setting. 1. Triple negative breast cancer patients must have received two lines of chemotherapy in the metastatic setting. 2. ER+/ PR+, ER-/PR+, and ER+/PR- must have received prior Cyclin Dependent Kinase 4/6 Inhibitor in combination with Aromatase Inhibitor or fulvestrant. However, ER+/Her2 overexpressed patients are not required to have received CDK 4/6 inhibitor. 3. Her2 overexpressed breast cancer must have had prior trastuzumab/per (in the neoadjuvant/adjuvant or metastatic setting, and prior Ado-trastuzumab TDM1 therapy. 9\. Adequate organ function determined within 14 days prior to enrollment, defined as follows: * Absolute neutrophil (ANC) \>1.5 x 109/L * Platelet count\>50 x 109/L * Hemoglobin\>8 g/dL * Serum creatinine \<2.0 x upper limit of normal * Serum bilirubin \< 2.0 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level \> 2.0 x ULN * Aspartate aminotransferase (AST) \<2.5 x ULN OR \<5 x ULN for subject with liver metastases * Alanine aminotransferase (ALT) \<2.5 x ULN OR \<5 x ULN for subject with liver metastases * International normalization ratio (INR) or prothrombin time (PT) \<1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and partial thromboplastin time (PTT)/activated PTT (aPTT) is within therapeutic range of intended use of anticoagulants * Lactate dehydrogenase (LDH) levels ≤ 1.5 X upper limit of normal (ULN) within 28 days prior to enrollment * Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If the urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * ECOG performance status of 0, 1 or 2. Exclusion Criteria: <!-- --> 1. \> 4 Clinically active cerebral metastases. Subjects cerebral metastases may be enrolled, provided that there are less than 4 lesions as these may serve as a site of pallative SBRT 2. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. 3. Any active autoimmune disease that in the judgement of the PI or sub-I could be significantly worsened by pembrolizumab 4. Evidence of clinically significant immunosuppression such as the following: * diagnosis of immunodeficiency; * concurrent opportunistic infection; * receiving systemic immunosuppressive therapy (\> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses \> 20 mg/day of prednisone or equivalent Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study. 5. Subject has known sensitivity to any of the products or components to be administered during dosing 6. Known human immunodeficiency virus (HIV) disease. 7. Known acute or chronic hepatitis B or hepatitis C infection. 8. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease. 9. Has a known history of active Bacillus tuberculosis. 10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 11. Those patients who would not otherwise have an indication for palliative SBRT 12. Prior therapy with tumor vaccine (unless administered in the adjuvant setting). 13. Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study. 14. Expected to require other cancer therapy while on study with the exception of local radiation treatment to the site of bone and other metastasis for palliative pain management. Concurrent endocrine therapy or trastuzumab therapy is allowed if clinically indicated. Concurrent bone modifying agents (including denosumab or zoledronic acid) is allowed for patients with bone metastases. 15. Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment or 4 months after the last dose of pembrolizumab 16. Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment or 4 months after the last dose of pembrolizumab, whichever is later. Note: Women not of childbearing potential are defined as: * postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women \< 45 years of age a high follicle stimulating hormone follicule stimulating hormone \[FSH\] level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.); OR * have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR * has a congenital or acquired condition that prevents childbearing. 17. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.