Single center, non-randomized, Phase 0 study. Sacituzumab Govitecan given preoperatively, followed by craniotomy with surgery or biopsy of brain tumors (GBM and metastatic brain tumors from Breast) and intraoperative tissue collection will follow with contemporaneous CSF (depending on tumor location) and whole blood (serum) sampling.

Inclusion Criteria:

• At least 18 years of age
• Histologically or cytologically documented breast cancer (Cohort A) with known or suspected parenchymal brain metastases.
• Recurrent glioblastoma (Cohort B) with documented progression by RANO criteria following standard combined modality treatment with radiation and temozolomide.
• Plans to undergo craniotomy as part of standard of care. Patients emergently needing surgical debulking due to symptoms of their disease are not eligible.
• Recovered from toxicities of prior therapy to grade 0 or 1
• ECOG performance status ≤ 2.
• Life expectancy of at least 3 months.
• Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN);
• Adequate renal function: calculated creatinine clearance ≥30mL/minute according to the Cockcroft and Gault formula
• Acceptable hematologic status (without hematologic support)
• ANC ≥1500 cells/uL
• Platelet count ≥100,000/uL
• Hemoglobin ≥9.0 g/dL
• All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.

Exclusion Criteria:

• The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.

• The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.

• The subject is unable to undergo MRI scan (eg, has pacemaker).

• The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).

• Patients whose only lesion undergoing resection has received stereotactic radiation within the past 3 months

• The subject has received any of the following prior anticancer therapy:

  • Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
  • Prior treatment with Sacituzumab Govitecan

• Patients receiving UGT1A1 (Uridine diphosphate glucuronosyl transferase 1A1) inhibitors or inducers.

• History of significant cardiovascular disease, defined as:

  • Congestive heart failure greater than New York Heart Association (NYHA) Class II according to the NYHA Functional Classification.
  • Unstable angina or myocardial infarction within 6 months before enrollment.
  • Serious cardiac arrhythmia.

• Clinically significant ECG abnormality, including:

  • Marked Baseline prolonged QT/QTc interval (ie, a repeated demonstration of a QTc interval >500 ms) demonstrated on ECG at Screening.
  • History of risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome).

• Any medical or other condition which, in the opinion of the Investigator, causes the subject to be medically unfit to receive Sacituzumab Govitecan, or unsuitable for any other reason.