Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer Who Have Received Endocrine Therapy

Study Overview
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Brief Summary
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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 current 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).

Official Title
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A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Hormone Receptor-Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) (HER2 IHC0 or HER2-low [IHC 1+, IHC 2+/ISH-]) Inoperable, Locally Advanced, or Metastatic Breast Cancer and Have Received Endocrine Therapy

Conditions
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Locally Advanced or Unresectable Metastatic Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy
* Drug: Paclitaxel
* Drug: Nab-paclitaxel
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Able to understand and give written informed consent. Must have adequate tumor tissue sample from locally recurrent or metastatic site. Documented evidence of HR+ metastatic breast cancer (mBC) confirmed with the most recently available tumor biopsy 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 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 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 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 or use of any investigational device or drug either within 5 half-lives or 28 days prior to randomization, whichever is longer. 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/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacituzumab Govitecan-hziy (SG)<br>Participants will receive SG at a dose of 10 mg/kg infusion on Days 1 and 8 of a 21-day cycle. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously<br>* Other names: IMMU-132;|
| Active Comparator: Treatment of Physician's Choice (TPC)<br>Participants will receive TPC determined prior to randomization to 1 of the 3 allowed regimens: paclitaxel 80 mg/m^2 over 1 hour (± 10 minutes) on Days 1, 8, and 15 of a 28-day cycle. nab-Paclitaxel 100 mg/m^2 over 30 minutes (± 10 minutes) on Days 1, 8, and 15 of a 28-day cycle. capecitabine at 1000-1250 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period of a 21-day cycle. | Drug: Paclitaxel<br>* Administered intravenously<br>* Other names: Taxol®;Drug: Nab-paclitaxel<br>* Administered intravenously<br>* Other names: Abraxane®;Drug: Capecitabine<br>* Administered orally<br>* Other names: Xeloda®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Up to approximately 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization until the date of death from any cause. | Until death, up to approximately 60 months | 
| Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 | 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. | Until progression, up to approximately 60 months | 
| 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 | 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. | Baseline, Week 16 | 
| Time to Deterioration in Version 3.0 EORTC-QLQ-C30 Scores | 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. | Up to approximately 60 months | 
| Progression Free Survival (PFS) as Assessed by Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 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. | Until progression or death, up to approximately 60 months | 
| Objective Response Rate (ORR) as Assessed by Investigator per RECIST Version 1.1 | 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. | Up to approximately 60 months | 
| Duration of Response (DOR) as Assessed by BICR and Investigator 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 objective PD or death from any cause (whichever comes first). | Until progression or death, up to approximately 60 months | 
| 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 |