Testing Sacituzumab Govitecan Therapy in Patients With HER2-Negative Breast Cancer and Brain Metastases

Inclusion Criteria:

• Participants must have histologically confirmed HER2-negative (per 2018 AmericanSociety of Clinical Oncology [ASCO]/College of American Pathologists [CAP] jointguideline) invasive breast cancer that has metastasized to the brain. NOTE:Pathology report must confirm HER2-negative invasive breast cancer. Brain metastasesmust be confirmed by radiology report

• Participants must have an magnetic resonance imaging (MRI) of the brain within 28days prior to registration and must have central nervous system metastases with atleast one measurable brain metastasis >= 1.0 cm in size (per RANO-BM) that has notbeen irradiated, or has progressed despite prior radiation therapy (in the opinionof the treating physician). In the rare case that a previously irradiated brainmetastasis is the sole target lesion and if there is concern about possibleradiation necrosis, patient is eligible only if there is clear progression in thepreviously radiated lesion. Computed tomography (CT) of the head cannot substitutefor brain MRI. All central nervous system (CNS) disease must be assessed anddocumented on the S2007 Brain Metastases Baseline Tumor Assessment Form

• Participants may have measurable or non-measurable extracranial disease. Allmeasurable disease must be assessed within 28 days prior to registration; allnon-measurable disease must be assessed within 42 days prior to registration.Participants are NOT required to have extracranial disease, but must have scans doneto document disease status at baseline. All extracranial disease must be assessedand documented on the Baseline Tumor Assessment Form (Response Evaluation Criteriain Solid Tumors [RECIST] 1.1). NOTE: Brain lesions should not be included on theBaseline Tumor Assessment Form (RECIST 1.1) for this study

• Participants must have had CNS progression after previous CNS-directed therapy (radiation therapy, surgery, or any combination of therapy)

• Participants must have resolution of adverse event(s) of the most recent priorsystemic anti-cancer therapy to < grade 2, with the exception of alopecia and =<grade 2 neuropathy, which are allowed

• Participants with a prior or concurrent malignancy whose natural history ortreatment (in the opinion of the treating physician) does not have the potential tointerfere with the safety or efficacy assessment of the investigational regimen areeligible for this trial

• Participants must have Zubrod performance status 0 or 1

• Participants must have history and physical exam obtained within 21 days prior toregistration

• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 21 days prior toregistration)

• Platelet count >= 100,000/mcL (obtained within 21 days prior to registration)

• Hemoglobin >= 9.0 g/dL (obtained within 21 days prior to registration)

• Total bilirubin =< 1.5 times institutional upper limit of normal (ULN) (obtainedwithin 21 days prior to registration)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 xinstitutional ULN (obtained within 21 days prior to registration)

• Participants must have a serum creatinine =< 1.5 times the institutional upper limitof normal (IULN) OR measured OR calculated creatinine clearance >= 30 mL/min usingthe following Cockcroft-Gault Formula. This specimen must have been drawn andprocessed within 21 days prior to registration

• Participants must have adequate cardiac function. Participants with known history orcurrent symptoms of cardiac disease, or history of treatment with cardiotoxicagents, must have a clinical risk assessment of cardiac function using the New YorkHeart Association Functional Classification, and must be class 2B or better

• Participants must be offered the opportunity to participate in specimen banking.With participant consent, specimens must be collected and submitted via theSouthwest Oncology Group (SWOG) Specimen Tracking System

• Participants must be informed of the investigational nature of this study and mustsign and give informed consent in accordance with institutional and federalguidelines

Exclusion Criteria:

• Participants must not have had more than 2 seizures within 28 days prior toregistration

• Participants must not have received systemic therapy (including small-moleculekinase inhibitors) or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 7 daysprior to registration

• Participants must not have received anti-cancer biologic agents (antibodies, immunemodulators, vaccines, cytokines) within 21 days prior to registration

• Participants must not have received nitrosoureas or mitomycin C within 42 days,metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxicchemotherapy within 28 days prior to registration

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviralagents that are strong CYP3A4 inhibitors or inducers and who are unwilling or unableto change to antiretroviral therapies without such interactions are ineligiblebecause of the potential for pharmacokinetic interactions with sacituzumab govitecan (IMMU-132)

• Due to potential drug interactions of anti-retroviral drugs with sacituzumabgovitecan (IMMU-132), participants must not have known active or chronic hepatitis Bvirus (HBV) infection, requiring suppressive therapy or known active hepatitis Cvirus (HCV) infection. Participants with a known history of HCV infection must havebeen treated and cured

• Participants must not have received enzyme-inducing anti-epileptic agents (e.g.,carbamazepine, phenytoin, phenobarbital, primidone) within 7 days prior toregistration or within 14 days of planned start of cycle 1, day 1 treatment, andparticipants must not be planning to receive enzyme-inducing anti-epileptic agents (e.g., carbamazepine, phenytoin, phenobarbital, primidone) for the duration ofprotocol treatment

• Participants must not be receiving warfarin (or other coumarin derivatives) at timeof registration or be planning to receive warfarin (or other coumarin derivatives)for the duration of protocol treatment. Participants who are able to switch to lowmolecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) prior to dateof registration (and plan to remain off of warfarin or other coumarin derivatives)for the duration of protocol treatment) are eligible

• Patients must not be receiving or be planning to receive concomitantly any otheranti-cancer therapy, including endocrine therapy. Note: Concomitant hormonereplacement therapy is allowed

• Participants must not have a condition requiring ongoing systemic treatment withcorticosteroids (> 4 mg daily dexamethasone [or bioequivalent]) or otherimmunosuppressive medications within 7 days prior to the baseline MRI.Corticosteroids administration must be stable and planned to remain =< 4 mg dailyfor the duration of protocol treatment. However, use of corticosteroids for clinicalsymptoms is allowed based upon treating physician discretion

• Participants must not have uncontrolled diabetes in the opinion of the treatinginvestigator 21 days prior to registration

• Participants must not be pregnant or nursing. Women of reproductive potential musthave a negative serum or urine pregnancy test within 7 days prior to registration.Women and men of reproductive potential must have agreed to use an effectivecontraceptive method for the duration of protocol treatment and for at least 6months after the last dose of sacituzumab govitecan (IMMU-132). A woman isconsidered to be of "reproductive potential" if she has had menses at any time inthe preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intendedto prevent pregnancy (or with a side-effect of pregnancy prevention) defined as ahysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at anypoint a previously celibate participant chooses to become heterosexually activeduring the time period for use of contraceptive measures outlined, he/she isresponsible for beginning contraceptive measures