Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to assess and compare the efficacy and safety of sacituzumab govitecan-hzi versus treatment of physician's choice (TPC) in participants with hormonal receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC).

Official Title
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Phase 3 Study of Sacituzumab Govitecan (IMMU-132) Versus Treatment of Physician's Choice (TPC) in Subjects With Hormonal Receptor-Positive (HR+) Human Epidermal Growth Factor Receptor 2 (HER2) Negative Metastatic Breast Cancer (MBC) Who Have Failed at Least Two Prior Chemotherapy Regimens

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy
* Drug: Eribulin
* Drug: Capecitabine
* Drug: Gemcitabine
* Drug: Vinorelbine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented evidence of hormone receptor-positive human epidermal growth factor receptor 2 negative (HER2-negative) (hormonal receptor-positive (HR+)/HER2-) metastatic breast cancer (MBC) confirmed. Refractory to or relapsed after at least 2, and no more than 4, prior systemic chemotherapy regimens for metastatic disease: At least 1 taxane in any setting. At least 1 prior anticancer hormonal treatment in any setting. At least 1 cyclin-dependent kinase inhibitor 4/6 in any setting. Eligible for one of the chemotherapy options listed in the TPC arm. Documented disease progression after the most recent therapy. Adequate bone marrow function (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500 per mm^3, platelets ≥ 100,000 per mm^3). Adequate renal function: calculated creatinine clearance ≥ 30 mL/minute according to the Cockcroft and Gault formula . Adequate liver function (bilirubin ≤ 1.5 institutional upper limit of normal (IULN), or ≤ 3 IULN for individuals with documented Gilbert's syndrome, aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x IULN (in the case of liver metastases ≤ 5.0 x IULN)). Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta human chorionic gonadotropin (ß-hCG)). Key Exclusion Criteria: Previous treatment with topoisomerase 1 Inhibitors as a free form or as other formulations. History of significant cardiovascular disease or clinically significant electrocardiogram (ECG) abnormality. Active serious infection requiring antibiotics. Any medical or other condition which, in the opinion of the Investigator, causes the individual to be medically unfit to receive sacituzumab govitecan or unsuitable for any reason. Locally advanced MBC (stage IIIc) in individuals who are candidates for curative intent therapy at the time of study enrollment. 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<br>Participants will receive sacituzumab govitecan-hziy 10 mg/kg via intravenous (IV) injection administered on Day 1 and Day 8 of a 21-day cycle. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously<br>* Other names: GS-0132;|
| Active Comparator: Treatment of Physician's Choice (TPC)<br>Participants will receive TPC determined prior to randomization from one of the following single-agent treatment: Dosing per National Comprehensive Cancer Network (NCCN) guidelines (with dose modifications for if toxic) Eribulin: 1.4 mg/m^2 for North American sites, 1.23 mg/m^2 for European sites) via IV on Days 1 and 8 of a 21-day cycle Capecitabine: 1000-1250 mg/m^2 orally twice daily for 2 weeks followed by a 1-week rest period given as a 21-day cycle Gemcitabine: 800-1200 mg/m^2 via IV on Days 1, 8, and 15 of each 28-day cycle or per institution Vinorelbine: 25 mg/m^2 via IV on Day 1 weekly cycle per institution | Drug: Eribulin<br>* Administered intravenously per NCCN guidelines<br>Drug: Capecitabine<br>* Administered orally per NCCN guidelines<br>Drug: Gemcitabine<br>* Administered intravenously per NCCN guidelines<br>Drug: Vinorelbine<br>* Administered intravenously per NCCN guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurs first) according to blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). | Up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants who have a best overall response of either Complete Remission (CR) or Partial Response (PR) that is confirmed ≥ 4 weeks later according to BICR using RECIST 1.1. | Up to approximately 3 years | 
| Overall Survival (OS) | OS is defined as the time from the date of randomization to the date of death from any cause. | Up to approximately 5 years | 
| Duration of Response (DOR) | DOR is defined as the time from the date a response was first documented until the date of the first documentation of disease progression or date of death (whichever occurs first). | Up to approximately 3 years | 
| Clinical Benefit Rate (CBR) | CBR is defined as best overall response of CR or PR or durable stable disease (duration of SD ≥ 6 months after randomization). | Up to approximately 3 years | 
| Time to Deterioration (TTD) of Global Health Status/Quality of Life (QoL) Scale as Measured by European Organization for Research and Treatment of Cancer Quality of Life for Cancer Patients, Core Questionnaire Version 3.0 (EORTC QLQ-C30) | The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant). Deterioration is defined as greater than or equal to 10 points worsening from baseline in the global health status/QoL scale. | Up to approximately 3 years | 
| TTD of Pain Score as Measured by EORTC QLQ-C30 | The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant). Deterioration is defined as greater than or equal to 10 points worsening from baseline in the pain score. | Up to approximately 3 years | 
| TTD of Fatigue Score as Measured by EORTC QLQ-C30 | The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant). Deterioration is defined as greater than or equal to 10 points worsening from baseline in the fatigue score. | Up to approximately 3 years | 
| Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) |  | Up to approximately 3 years | 
| Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) |  | Up to approximately 3 years | 
| Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities |  | Up to approximately 3 years | 
| Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status |  | Baseline, Up to approximately 3 years |