Sacituzumab Govitecan and Zimberelimab w/SRS in the Management of Metastatic Triple Negative Breast Cancer With Brain Metastases

Inclusion Criteria:

• Provision of signed and dated Informed Consent Form (ICF).

• Stated willingness to comply with all study procedures and availability for theduration of the study.

• Age ≥ 18.

• Triple negative breast cancer; to fulfill the requirement of triple negativedisease, a breast cancer must express (≤ 10%), by immunohistochemistry (IHC), of thehormone receptors (estrogen receptor [ER] and progesterone receptor [PR]).

• Breast cancer as documented by extracranial tumor biopsy with brain metastasesdocumented from MRI brain imaging or intracranial surgical pathology.

• Eligible for Stereotactic radiosurgery (SRS) to brain metastases or to thepost-operative bed.

• Measurable brain disease per RANO-BM criteria1 that can be measured in at least onedimension as ≥ 0.5 cm for both intact brain metastases and post-operative cavities.

• Maximum diameter of the largest intact brain metastases ≤ 4 cm.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

• Symptomatic patients having undergone surgery or on stable doses of steroids ≤ 8mg/day dexamethasone will be enrolled.

• Prior treatment with taxane based chemotherapy with anthracyclines.

• Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatmentwill be allowed if active measurable disease has not previously been treated withradiation therapy.

• Women of childbearing potential (WOCBP) must have a negative serum or urinepregnancy test within 24 hours prior to the administration of each dose of studyagent.

• Male and female patients of childbearing potential who engage in heterosexualintercourse must agree to use specified method(s) of contraception.

Exclusion Criteria:

• Presence of leptomeningeal disease.

• Women who are pregnant or breastfeeding.

• Known history of HIV-1 or 2 with detectable viral load.

• Active, known, or suspected autoimmune disease. Patients with an autoimmuneparaneoplastic syndrome requiring concurrent immunosuppressive treatment areexcluded. Exceptions are patients with type I diabetes mellitus, hypothyroidism onlyrequiring thyroid replacement therapy, skin disorders (such as vitiligo, psoriasis,or alopecia) not requiring systemic treatment, or conditions not expected to recurin the absence of an external trigger are permitted to enroll.

• History of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease.

• Met any of the following criteria for cardiac disease:

1. Myocardial infarction or unstable angina pectoris within 6 months of enrollment

2. History of serious ventricular arrhythmia (ie, ventricular tachycardia orventricular fibrillation), high-grade atrioventricular block, or other cardiacarrhythmias requiring antiarrhythmic medications (except for atrialfibrillation that is well controlled with antiarrhythmic medication); historyof QT interval prolongation

3. New York Heart Association (NYHA) Class III or greater congestive heart failureor left ventricular ejection fraction of < 40%

• Any patient requiring supplemental oxygen therapy.

• Have an active serious infection requiring antibiotics.

• Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)or GI perforation within 6 months of enrollment.

• Patients with prior history of non-breast cancer malignancies are excluded except inthe case of adequately treated basal cell cancer, squamous cell skin cancer, chroniclymphocytic leukemia, or other cancers in remission not receiving active therapy for ≥ 2 years.

• Known medical condition that, in the investigator's opinion, would increase the riskassociated with study participation or study drug(s) administration or that wouldinterfere with the interpretation of safety results.

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

• Have had a prior anticancer biologic agent within 4 weeks prior to enrollment orhave had prior chemotherapy, targeted small molecule therapy within 2 weeks prior toenrollment and have not recovered.

• Have previously received topoisomerase 1 inhibitors in the setting of brainmetastases.

• Use of other investigational drugs (drugs not marketed for any indication) within 28days or 5 half-lives (whichever is longer) of first dose of study drug.

• Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In patients with ahistory of HBV or HCV, patients with detectable viral loads will be excluded.

• History of allergy or hypersensitivity to any of the study drugs or study drugcomponents.

• Prisoners or individuals who are involuntarily incarcerated.

• Individuals who are compulsorily detained for treatment of either a psychiatric orphysical (eg, infectious disease) illness.