A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan Versus Treatment of Physician*s Choice in Patients With Previously Untreated, Locally Advanced, Inoperable or Metastatic Triple-Negative Breast Cancer Whose Tumors Do Not Express PD-L1 or in Patients Previously Treated With Anti-PD-(L)1 Agents in the Early Setting Whose Tumors Do Express PD-L1.

Patients must meet all of the following inclusion criteria to be eligible for
participation in this study (no waivers for patient eligibility will be offered
or permitted):
1) Female or male patients, regardless of race and ethnic group, who are 18
years of age or older, able to understand and give written informed consent.
2) Patients with locally advanced, inoperable, or metastatic TNBC who have not
received previous systemic therapy for advanced disease and whose tumors are
PD-L1 negative at screening. Alternatively, patients whose tumors are PD-L1
positive at screening will be eligible if they received an anti-programmed
death (ligand) 1 (anti-PD-[L]1) agent (ie, checkpoint inhibitor) in the
adjuvant or neoadjuvant setting or if they cannot be treated with an
anti-PD-(L)1 agent due to a comorbidity.
a) Patients must have completed treatment for Stage I-III breast cancer, if
indicated, and >= 6 months must have elapsed between completion of treatment
with curative intent (eg, date of primary breast cancer surgery or date of last
(neo)adjuvant chemotherapy administration [including anti-PD-(L)1 treatment],
whichever occurred last) and first
documented local or distant disease recurrence. Dates of postoperative
radiotherapy are not included in this calculation.
i) Patients who received taxane, gemcitabine, or platinum agents in the
(neo)adjuvant setting can be treated with same class of chemotherapy (taxane or
gemcitabine/carboplatin) if >= 12 months have elapsed between the completion of
treatment with curative intent (eg, date of primary breast tumor surgery or
date of last (neo)adjuvant chemotherapy administration, whichever occurred
last) and first documented local or distant disease recurrence.
ii) Patients enrolled should have received prior anthracycline in the
(neo)adjuvant setting or be considered not eligible for anthracyclines as
assessed by the treating physician.
b) Patients presenting with de novo metastatic TNBC are eligible for this study.
c) TNBC status and tumor PD-L1 CPS will be confirmed centrally on a recent or
archival tumor specimen. Patients must have histologically or cytologically
documented TNBC, according to current ASCO/CAP criteria, defined as negative
for ER, progesterone receptor, and HER2. Patients initially diagnosed with
hormone receptor-positive or HER2-positive breast cancer must have central
confirmation of TNBC in a tumor biopsy obtained from a local recurrence or
distant metastasis prior to entry. Tumor combined positive score (CPS) < 10
using the PD-L1 IHC 22C3 assay will be required for eligibility. Alternatively,
patients with tumor CPS >= 10 will be eligible if they received an
anti--PD--(L)1 agent (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant
setting or if they cannot be treated with an antiPD-(L)1 agent due to a
comorbidity.
d) Patients must have measurable disease by CT or MRI as per RECIST Version 1.1
criteria as evaluated locally. Tumor lesions situated in a previously
irradiated area are considered measurable if unequivocal progression has been
documented in such lesions since radiation.
3) Have provided representative formalin-fixed paraffin-embedded (FFPE) tumor
specimen in blocks (preferred) or have at least 20 to 25 freshly sectioned
unstained slides from fresh biopsy tissue (preferred) or archival tissue block
for central testing of ER, progesterone receptor, HER2, and PD-L1 and
additional biomarker testing. A baseline biopsy is required if archival tissue
is not available and this procedure must be performed prior to the first dose
of study treatment and after the patient provides written informed consent.
Fine needle aspirates and bone biopsies are not suitable samples.
Note: Tumor tissue quality must be confirmed by the central laboratory.
Submission of another tumor specimen may be required if provided specimen is
not adequate for assessment. A discussion with the medical monitor is required
if only 15 to 19 unstained slides are available and it is not clinically
feasible to obtain a new biopsy.
4) ECOG performance status score of 0 or 1
5) Life expectancy >= 3 months
6) Recovered from major surgery for >= 2 weeks
7) Adequate hematologic counts without transfusional or growth factor support
within 2 weeks of study treatment initiation (hemoglobin >= 9 g/dL, ANC >=
1500/mm3, and platelets >= 100,000/µL).
8) Adequate hepatic function (bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN or
<= 5 x ULN if known liver metastases, and serum albumin > 3 g/dL).
9) Creatinine clearance >= 30 mL/min as assessed by the Cockcroft-Gault
equation.
10) International Normalized Ratio (INR)/PT and PTT or aPTT <= 1.5 ULN unless
patient is currently receiving therapeutic anticoagulant therapy.
11) Male patients and female patients of childbearing potential who engage in
heterosexual intercourse must agree to use protocol-specified method(s) of
contraception as described in protocol Appendix 3.
12) Patients with HIV must be on antiretroviral therapy (ART) and have a
well-controlled HIV infection/ disease

Patients who meet any of the following exclusion criteria are not eligible to
be enrolled in this study (no waivers for patient eligibility will be offered
or permitted):
1) Positive serum pregnancy test or women who are lactating.
2) Known or severe (>= Grade 3) hypersensitivity or allergy to sacituzumab
govitecan and/or the chemotherapy regimen of choice in the TPC arm (eg,
nab-paclitaxel, paclitaxel, gemcitabine, or Carboplatin), their metabolites, or
formulation excipient.
3) Requirement for ongoing therapy with or prior use of any prohibited
medications listed in section 5.6.1 of the protocol.
4) Patients may not have received systemic anticancer treatment (with the
exception of endocrine therapy) within the previous 6 months or radiation
therapy within 2 weeks prior to enrollment. Patients must have recovered (ie, >
Grade 2 is considered not recovered) from AEs due to a previously administered
agent at the time of study entry.
- Note: patients with any grade neuropathy or alopecia are an exception to this
criterion and will qualify for the study.
- Note: if patients received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.
5) Patients may not be participating in a study with an investigational agent
or investigational device within 4 weeks prior to randomization. Patients
participating in observational studies are eligible.
6) Have previously received topoisomerase 1 inhibitors or antibody drug
conjugates containing a topoisomerase inhibitor.
7) Have an active second malignancy.
8) Have known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Patients with previously treated brain metastases may
participate (with the exception of those treated with chemotherapy) provided
they have stable CNS disease (defined as radiographic stability demonstrated
with a minimum of 2 posttreatment brain imaging assessments; one performed
during screening) for at least 4 weeks prior to enrollment and all neurologic
symptoms have returned to baseline, have no evidence of new or enlarging brain
metastases, and have also been clinically stable for at least 2 weeks while
taking <= 10 mg/day of prednisone or its equivalent. All patients with
carcinomatous meningitis are excluded regardless of clinical stability.
9) Met any of the following criteria for cardiac disease:
a) Myocardial infarction or unstable angina pectoris within 6 months of
enrollment.
b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or
ventricular fibrillation), high-grade atrioventricular block, or other cardiac
arrhythmias requiring antiarrhythmic medications (except for atrial
fibrillation that is well controlled with antiarrhythmic medication); history
of QT interval prolongation.
c) New York Heart Association Class III or greater congestive heart failure or
known left ventricular ejection fraction of < 40%.
10) Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn*s
disease) or GI perforation within 6 months of enrollment.
11) Have active serious infection requiring antibiotics.
12) Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or
Multicentric Castleman Disease.
13) Have active HBV (defined as having a positive HbsAg test) or HCV.
a) For patients with a history of HBV infection, a hepatitis B core antibody
test should be conducted at screening. If positive, hepatitis B DNA testing
will be performed and if active HBV infection is ruled out, the patient may be
eligible.
b) Patients who are HCV antibody positive with undetectable HCV viral load may
be eligible.
14) Have other concurrent medical or psychiatric conditions that, in the
investigator*s opinion, may be likely to confound study interpretation or
prevent completion of study procedures and follow-up examinations.
15) Has received a live vaccine within 30 days prior to randomization.