A PHASE II TRIAL OF SACITUZUMAB GOVITECAN (IMMU-132) (NSC #820016) FOR PATIENTS WITH HER2-NEGATIVE BREAST CANCER AND BRAIN METASTASES

This phase II trial studies the effect of sacituzumab govitecan in treating patients with
HER2-negative breast cancer that has spread to the brain (brain metastases). Sacituzumab
govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called
govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific
molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers govitecan
to kill them. Giving sacituzumab govitecan may shrink the cancer in the brain and/or extend
the time until the cancer gets worse.

Inclusion Criteria:

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

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

- Participants may have measurable or non-measurable extracranial disease. All
measurable disease must be assessed within 28 days prior to registration; all
non-measurable disease must be assessed within 42 days prior to registration.
Participants are NOT required to have extracranial disease, but must have scans done
to document disease status at baseline. All extracranial disease must be assessed and
documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in
Solid Tumors [RECIST] 1.1). NOTE: Brain lesions should not be included on the Baseline
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 prior
systemic 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 or treatment
(in the opinion of the treating physician) does not have the potential to interfere
with the safety or efficacy assessment of the investigational regimen are eligible for
this trial

- Participants must have Zubrod performance status 0 or 1

- Participants must have history and physical exam obtained within 21 days prior to
registration

- Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 21 days prior to
registration)

- 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) (obtained
within 21 days prior to registration)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x
institutional ULN (obtained within 21 days prior to registration)

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

- Participants must have adequate cardiac function. Participants with known history or
current symptoms of cardiac disease, or history of treatment with cardiotoxic agents,
must have a clinical risk assessment of cardiac function using the New York Heart
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 the Southwest
Oncology Group (SWOG) Specimen Tracking System

- Participants must be informed of the investigational nature of this study and must
sign and give informed consent in accordance with institutional and federal guidelines

Exclusion Criteria:

- Participants must not have had more than 2 seizures within 28 days prior to
registration

- Participants must not have received systemic therapy (including small-molecule kinase
inhibitors) or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 7 days prior to
registration

- Participants must not have received anti-cancer biologic agents (antibodies, immune
modulators, 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 cytotoxic
chemotherapy within 28 days prior to registration

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

- Due to potential drug interactions of anti-retroviral drugs with sacituzumab govitecan
(IMMU-132), participants must not have known active or chronic hepatitis B virus (HBV)
infection, requiring suppressive therapy or known active hepatitis C virus (HCV)
infection. Participants with a known history of HCV infection must have been treated
and cured

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

- Participants must not be receiving warfarin (or other coumarin derivatives) at time of
registration or be planning to receive warfarin (or other coumarin derivatives) for
the duration of protocol treatment. Participants who are able to switch to low
molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) prior to date of
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 other
anti-cancer therapy, including endocrine therapy. Note: Concomitant hormone
replacement therapy is allowed

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

- Participants must not have uncontrolled diabetes in the opinion of the treating
investigator 21 days prior to registration

- Participants must not be pregnant or nursing. Women of reproductive potential must
have 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 effective
contraceptive method for the duration of protocol treatment and for at least 6 months
after the last dose of sacituzumab govitecan (IMMU-132). A woman is considered to be
of "reproductive potential" if she has had menses at any time in the preceding 12
consecutive months. In addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
previously celibate participant chooses to become heterosexually active during the
time period for use of contraceptive measures outlined, he/she is responsible for
beginning contraceptive measures