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Lay Description

This is an international, multicenter, open-label, randomized, Phase 3 study in patients with

locally advanced, inoperable or metastatic triple-negative breast cancer (TNBC) who have not received previous therapy for advanced disease and whose tumors are either: PD-L1 negative at screening (defined using the PD-L1 IHC 22C3 assay as tumors with a combined positive score (CPS) < 10), OR PD-L1 positive at screening (defined using the PD-L1 IHC 22C3 assay as tumors with a CPS ≥ 10) if they previously received a checkpoint inhibitor in the adjuvant or neoadjuvant setting.

Category

  • Cancers and Other Neoplasms
IRB Number
20220197HU
NCT Number
ct.gov registration not required
Open to Enrollment
Yes

Eligibility

Eligible Ages
18
Eligible Genders
All
Accepts Healthy Volunteers

Inclusion Criteria

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 PDL1
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) inhibitor (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting.
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.
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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 {Allison 2020, Wolff 2018}{Allison 2020, Wolff 2018}. 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 inhibitor (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant
setting.
d) Patients must have measurable disease by CT or MRI as per RECIST Version 1.1
criteria (Appendix 6) 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.
4) ECOG performance status score of 0 or 1 (see Appendix 5).
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).
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8) Adequate hepatic function (bilirubin ≤ 1.5 ULN, AST and ALT ≤ 2.5  ULN or ≤ 5
 ULN if known liver metastases, and serum albumin > 3 g/dL).
9) Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation
{Cockcroft 1976}.
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 Appendix 3.
12) Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled
HIV infection/disease defined as:
a) Patients on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of
screening.
b) Patients on ART must have achieved and maintained virologic suppression
defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of
qualification (below the limit of detection) using the locally available assay at the
time of screening and for at least 12 weeks prior to screening.
c) Patients on ART must have been on a stable regimen, without changes in drugs or
dose modification, for at least 4 weeks prior to study entry (Day 1).
d) The combination ART regimen must not contain any medications that may
interfere with SN-38 metabolism.

Exclusion Criteria

Positive serum pregnancy test or women who are lactating (see Appendix 3).
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.
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4) Patients may not have received systemic anticancer treatment or surgery (whichever
occurred last) 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.
Note: patients with a history of malignancy that has been completely treated, with no
evidence of active cancer for 3 years prior to enrollment, or patients with surgically
cured tumors with low risk of recurrence (eg, non-melanoma skin cancer,
histologically confirmed complete excision of carcinoma in situ, or similar) are
allowed to enroll.
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 arehave 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
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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 HBsAgHbsAg 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.

Study Design

Arm Groups

Study Contact


Frances Crawford
(210) 450-5037
crawfordf1@uthscsa.edu

Sonia Creighton
(210) 450-1366
creighton@uthscsa.edu

Myrna Montenegro
(210) 450-5954
montenegro@uthscsa.edu

Courtney Nichols
(210) 450-1794
nicholsc2@uthscsa.edu

Mailbox Ctrc Regulatory Affairs
regaffapp@uthscsa.edu

Kathleen Rodriguez
(210) 450-1365
rodriguezk3@uthscsa.edu

Benjamin Schleif
(210) 450-1366
schleifb@uthscsa.edu

Morgan Seekatz
(210) 450-1133
seekatz@uthscsa.edu

Principal Investigator
Virginia Kaklamani