Purpose

The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by independently-reviewed Independent Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) previously treated with at least two systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and without brain metastasis at baseline.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple negative is defined as <1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization. - Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC. - Prior exposure to a taxane in localized or advanced/metastatic setting. - Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment. - Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Bone-only disease is not permitted. - At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy, radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade 1 or less (except alopecia and peripheral neuropathy). - At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks). - Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3). - Adequate renal and hepatic function (creatinine clearance [CrCL] > 60 mL/min, bilirubin ≤ 1.5 institutional upper limit of normal [IULN], aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin ≥3 g/dL). - Recovered from all toxicities to Grade 1 or less by National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v4.03 (except alopecia or peripheral neuropathy that may be Grade 2 or less) at the time of randomization. Participants with Grade 2 neuropathy are eligible but may not receive vinorelbine as TPC. - Participants with treated, non-progressive brain metastases, off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.

Exclusion Criteria

  • Women who are pregnant or lactating. - Women of childbearing potential or fertile men unwilling to use effective contraception during study and up to three months after treatment discontinuation in women of child-bearing potential and six months in males post last study drug. - Participants with Gilbert's disease. - Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while participants with other prior malignancies must have had at least a 3-year disease-free interval. - Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive, or hepatitis C positive. - Infection requiring antibiotic use within one week of randomization. - 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. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Sacituzumab Govitecan
Participants will receive sacituzumab govitecan on Days 1 and 8 of a 21-day treatment cycle for up to 29.6 months. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable adverse events (AEs).
  • Drug: Sacituzumab govitecan
    10 mg/kg administered as a slow intravenous (IV) infusion either by gravity or with an infusion pump. Infusion rate for the first 15 minutes will start with 50 mg/hour or less with a subsequent infusion of 100 to 200 mg/hour up to a maximum recommended rate (advanced every 15 to 30 minutes) of 500 mg/hour with a subsequent infusion of 1000 mg/hour.
    Other names:
    • IMMU-132
    • Trodelvy®
Active Comparator
Treatment of Physician's Choice (TPC)
Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
  • Drug: Eribulin
    Administered IV over 2 to 5 minutes at a dose 1.4 mg/m^2 at North American sites and 1.23 mg/m^2 at European sites on Days 1 and 8 of a 21-day cycle for up to 15.3 months. Lower doses will be administered on the same schedule to participants with moderate hepatic impairment (ie, Child-Pugh B; 0.7 mg/m^2 and 0.67 mg/m^2 for North American and European sites, respectively).
    Other names:
    • Halaven
  • Drug: Capecitabine
    1000 to 1250 mg/m^2 will be administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period for up to 10.6 months.
    Other names:
    • Xeloda
  • Drug: Gemcitabine
    800 to 1200 mg/m^2 will be administered IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle for up to 8.1 months.
    Other names:
    • Gemzar
  • Drug: Vinorelbine
    25 mg/m^2 will be administered as a weekly IV injection over 6-10 minutes for up to 11.5 months. Vinorelbine will not be allowed as TPC for any participant with Grade 2 neuropathy.
    Other names:
    • Navelbine

More Details

Status
Completed
Sponsor
Gilead Sciences

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.