Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients

Inclusion Criteria:

• Age older than 18

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Neurological function status 0, 1, 2

• Men and/or pre- or post-menopausal women with metastatic breast cancer with at least 2 intracranial untreated and measurable (≥ 5mm) metastases as visualized on brainMRI

• A diagnostic contrast enhanced MRI demonstrating at least 2 and no more than 10measurable lesions in the brain, (≥5mm in size), performed within two weeks prior totreatment

• Maximum diameter of treated lesions should be <4cm in size

• Have measurable disease based on RECIST 1.1. Lesions situated in a previouslyirradiated area are considered measurable if progression has been demonstrated insuch lesions.

• Patient needs to be able to understand and demonstrate willingness to sign a writteninformed consent document

• Prior SRS is permitted, however the lesions targeted for treatment on trial need tobe previously untreated by SRS

• Patients who have undergone prior subtotal resection are eligible providing thatresidual disease is <4cm in maximum diameter: the cavity will be treated as - - -Continuing a concurrent use of hormonal therapy or anti-Her2 neu therapy is allowed,if the patient exhibits brain metastases progression during these treatments

• Enrolled patients should have a two-week washout period from last systemic treatment

• The participant (or legally acceptable representative if applicable) provideswritten informed consent for the trial.

• Contraception duration of 120 days

• Adequate bone marrow reserve and liver function

Exclusion Criteria:

• Active connective tissue disorders, such as lupus or scleroderma requiring flaretherapy

• Patients who have undergone complete resection of all known brain metastases

• Inability to obtain histologic proof of breast cancer

• Target lesion metastasis within 5mm of the optic apparatus so that some portion ofthe optic nerve or chiasm would be included in the SRS field

• Has received prior radiotherapy within 2 weeks of start of study treatment.Participants must have recovered from all radiation-related toxicities, not requirecorticosteroids, and not have had radiation pneumonitis. A 1-week washout ispermitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

• Has received a live vaccine or live-attenuated vaccine within 30 days prior to thefirst dose of study drug. Administration of killed vaccines is allowed.

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study treatment.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of study drug.

• Has a known additional malignancy (second primary) that is progressing or hasrequired active treatment within the past 3 years. Note: Participants with basalcell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma insitu (e.g. cervical cancer in situ) that have undergone potentially curative therapyare not excluded.

• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of itsexcipients.

• Has active autoimmune disease that has required systemic treatment in the past 2years (i.e. with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment.

• Has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis.

• Has an active infection requiring systemic therapy..Has a known history of HumanImmunodeficiency Virus (HIV).

• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] isdetected) infection. Note: no testing for Hepatitis B and Hepatitis C is requiredunless mandated by local health authority.

• Has a known history of active TB (Bacillus Tuberculosis).

• Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of trial treatment.