Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Participants with Previously Untreated Locally Advanced, Inoperable (cannot be removed surgically), or Metastatic (spread to other locations in the body) Triple Negative Breast Cancer (breast cancer that does not have receptors for Oestrogen and progesterone hormones or HER2 proteins).
- Conditions
- Programmed cell death ligand 1 (PD-L1) negative metastatic triple-negative breast cancer or PD-L1-positive metastatic triple-negative breast cancer previously treated with an anti-PD-(L)1 agent in the curative setting.MedDRA version: 23.0Level: LLTClassification code 10084066Term: Triple negative breast cancer metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005743-79-ES
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 540
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) inhibitor (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting.
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.
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 427
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 113
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 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.
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method