Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases

Inclusion Criteria:

- Provides signed and dated informed consent

- Stated willingness to comply with all study procedures and availability for the
duration of the study

- Age 18 or older

- Breast cancer with brain metastases, as documented by extracranial tumor biopsy with
MRI brain imaging or intracranial surgical pathology revealing brain metastases

- 10 or less brain metastases eligible for SRS to brain metastases or to the
post-operative bed

- Maximum diameter of the largest intact brain metastases ≤ 4 cm

- Eastern Cooperative Oncology Group performance status 0 to 2

- Prior treatment with taxane based chemotherapy with anthracyclines (if appropriate)

- A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of
intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation
should be made available and submitted to the central lab for correlative studies. If
attempts to obtain archival tissue are unsuccessful the patient may be enrolled.

- Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will
be allowed if active measurable disease has not previously been treated with radiation
therapy

- Continuing concurrent use of hormonal therapy or HER2-targeted therapy is allowed if
the patient exhibits brain metastases progression during treatment

- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin)
within 24 hours prior to the administration of each dose of study agent.

- WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with study drug(s), plus 5 half-lives of study drug (half-life
up to 25 days), plus 30 days (duration of ovulatory cycle) for a total of 5 months
after treatment completion.

Exclusion Criteria:

- Presence of leptomeningeal disease

- Prior whole brain radiation therapy

- All toxicities attributed to prior anticancer therapy must have been resolved to Grade
1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) . Some
exceptions apply.

- Women who are pregnant or breastfeeding

- Active, known, or suspected autoimmune disease. Patients with an autoimmune
paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded.
Some exceptions apply.

- Prior therapy with antiPD-1, antiPD-L1, antiPD-L2, antiCD137, or antiCTLA-4 antibody
(including ipilimumab or any other antibody or drug specifically targeting T-cell
co-stimulation or checkpoint pathways)

- Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected drug-related pulmonary toxicity

- Any patient requiring supplemental oxygen therapy

- Patients with prior history of non-breast cancer malignancies are excluded except in
the case of adequately treated basal cell cancer, squamous cell skin cancer, chronic
lymphocytic leukemia, or other indolent diseases not requiring therapy

- Known medical condition that, in the investigator's opinion, would increase the risk
associated with study participation or study drug(s) administration or that would
interfere with the interpretation of safety results

- Major surgery or significant traumatic injury that has not been recovered from by 14
days before the initiation of study drug

- Current or prior participation in a study of an investigational agent or
investigational device within 2 weeks of first dose of study treatment

- Positive test for: a. Hepatitis B virus using Hepatitis B virus surface antigen
(Hepatitis B virus surface antigen) test b. Hepatitis C virus (HCV) using HCV
ribonucleic acid or HCV antibody test that indicates acute or chronic infection c.
Exception: Individuals with a positive test for HCV antibody but no detection of HCV
ribonucleic acid indicating no current infection are eligible

- Medical history of testing positive for HIV or AIDS. No HIV testing is required,
unless mandated by a local health authority.

- Inadequate hematologic function

- Inadequate hepatic function

- Inadequate pancreatic function

- History of allergy or hypersensitivity to any of the study drugs or study drug
components

- Individuals who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness