Breast cancer
Conditions
Interventions
Please refer to tables 1-3 of the Main ICF.
Sponsors
Gilead Sciences
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 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
Exclusion criteria
Exclusion criteria: 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 hav
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death (whichever comes first). | — |
Secondary
| Measure | Time frame |
|---|---|
| • OS is defined as the time from the date of randomization until death due to any cause. • ORR is defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response as assessed by BICR per RECIST Version 1.1. • DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive PD or death from any cause (whichever comes first) as assessed by BICR per RECIST Version 1.1. • TTR is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR per RECIST Version 1.1. • Incidence of treatment-emergent AEs (TEAEs) and clinical laboratory abnormalities. • Mean change from baseline in the physical functioning domain of the EORTC QLQ C30 at week 25 • TTD of fatigue domain of the EORTC QLQ-C30 is defined as the time between the date of randomization and the date of assessment at which a patient experienced a deterioration (ie, >= 10 points worsening from baseline in the fatigue domain) or death Exploratory End Points: • Correlation of clinical outcome (PFS, OS, ORR, and DOR) with baseline tumor Trop-2 expression • Correlation of clinical outcome (PFS, OS, ORR, and DOR) with tumor, tumor microenvironment, and blood biomarkers at baseline and post-SG treatment • Clearance of circulating tumor DNA upon SG treatment • Correlation of AEs to UGT1A1 status • Correlation of pharmacokinetics and immunogenicity of SG • Additional QOL end points include mean change from baseline, TTD (in addition to the subscales specified as secondary end points), time to improvement, proportion improved, and proportion worsened. | — |
Countries
Netherlands
Outcome results
None listed