Locally Advanced or Unresectable Metastatic Breast Cancer, Stage IV Breast Cancer
Conditions
Brief summary
The goal of this clinical study is to see if sacituzumab govitecan-hziy (SG) can improve life spans of people with HR+/HER2- metastatic breast cancer and their tumor does not grow or spread when compared to currently available standard treatments, such as paclitaxel, nab-paclitaxel or capecitabine. The primary objective is to compare the effect of SG relative to the treatment of physician's choice (TPC) on progression-free survival (PFS).
Interventions
DRUGSacituzumab Govitecan-hziy
Administered intravenously
DRUGPaclitaxel
Administered intravenously
DRUGNab-paclitaxel
Administered intravenously
DRUGCapecitabine
Administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Able to understand and give written informed consent. * Must have adequate tumor tissue sample preferably from locally recurrent or metastatic site. * Documented evidence of HR+ metastatic breast cancer (mBC) confirmed with the most recently available tumor biopsy preferably from a locally recurrent or metastatic site. * Documented evidence of HER2- status. * Documented PD by computed tomography (CT) or magnetic resonance imaging during or after the most recent therapy per RECIST v1.1 criteria. * Candidate for the first chemotherapy in the locally advanced or metastatic setting. * Eligible for capecitabine, nab-paclitaxel, or paclitaxel. * Individuals must have at least one of the following: * Disease progression on at least 2 or more previous lines of endocrine therapy (ET) with or without a targeted therapy in the metastatic setting. * Disease recurrence while on the first 24 months of starting adjuvant ET will be considered a line of therapy; these individuals will only require 1 line of ET in the metastatic setting. * Disease progression within 6 months of starting first-line ET with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor (if ineligible or if unable to access a CDK 4/6 inhibitor) in the metastatic setting. * Disease recurrence while on the first 24 months of starting adjuvant ET with CDK 4/6 inhibitor and if the individual is no longer a candidate for additional ET in the metastatic setting. * Individuals may have received prior targeted therapies, including but not limited to PARP inhibitors (for those with germline BRCA1 or BRCA2 mutations), phosphatidylinositol 3-kinase (PI3K) inhibitors (for those with PIK3CA mutations), or mammalian target of rapamycin (mTOR) inhibitors. However, individuals can no longer be candidates for additional endocrine treatment with or without targeted therapies. * Individuals with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease. * Demonstrates adequate organ function. * Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Key
Exclusion criteria
* Progressive disease within 6 months of completing (neo)adjuvant chemotherapy. * Locally advanced metastatic breast cancer (mBC) (Stage IIIc) in individuals who are candidates for curative intent therapy at the time of study enrollment. * Current enrollment in another clinical study and use of any investigational device or drug (drugs not marketed for any indication) either within 5 half-lives or 28 days prior to randomization, whichever is longer. * Use of investigational drugs in the category of Selective Estrogen Receptor Degraders are acceptable if last dose was longer than 14 days prior to randomization. * Received any prior treatment (including antibody-drug conjugate (ADC)) containing a chemotherapeutic agent targeting topoisomerase I. * Received any prior treatment with a trophoblast cell-surface antigen 2 (Trop-2)-directed ADC. * Have an active second malignancy. * Have an active serious infection requiring antibiotics. * Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). * Individuals positive for human immunodeficiency virus type 1/2 (HIV-1 or -2) with a history of Kaposi sarcoma and/or Multicentric Castleman Disease. * Have a positive serum pregnancy test or are breastfeeding for individuals who are assigned female at birth. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to approximately 29 months | PFS is defined as time from date of randomization until the date of first objective progressive disease (PD) or death from any cause, whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 | Until progression, up to approximately 60 months | ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response. |
| Change from Baseline in the Physical Functioning Domain Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30) at Week 16 | Baseline, Week 16 | The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants will be asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 4 (excellent), with a higher score representing a high QoL. |
| Time to Deterioration in Version 3.0 EORTC-QLQ-C30 Scores | Up to approximately 60 months | Time to deterioration from baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden. |
| Progression Free Survival (PFS) as Assessed by Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Until progression or death, up to approximately 60 months | PFS is defined as time from date of randomization until the date of first objective progressive disease (PD) by investigator assessment according to RECIST v1.1 or death from any cause, whichever comes first. |
| Overall Survival (OS) | Until death, up to approximately 60 months | OS is defined as the time from randomization until the date of death from any cause. |
| Duration of Response (DOR) as Assessed by BICR and Investigator per RECIST Version 1.1 | Until progression or death, up to approximately 60 months | DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of objective PD or death from any cause (whichever comes first). |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | First dose date up to 30 days post last dose, up to approximately 60 months | — |
| Percentage of Participants Experiencing Clinically Significant Laboratory and/or Vital Sign Abnormalities | First dose date up to 30 days post last dose, up to approximately 60 months | — |
| Objective Response Rate (ORR) as Assessed by Investigator per RECIST Version 1.1 | Up to approximately 60 months | ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Malaysia, Mexico, Poland, Portugal, Singapore, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed