Asian Study of Sacituzumab Govitecan (IMMU-132) in HR+/HER2- Metastatic Breast Cancer (MBC)

Study Overview
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Brief Summary
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The goal of this study is to compare the study drug, sacituzumab govitecan-hziy, versus doctors' treatment of choice in participants with HR+/HER2- metastatic breast cancer (MBC) who have failed at least 2 prior chemotherapy regimens.

Detailed Description
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Approximately 330 eligible participants will be randomly allocated to one of the following 2 treatment arms in a 1:1 ratio: Investigational Arm: Sacituzumab Govitecan-hziy 10 mg/kg via intravenous (IV) injection administered on Day 1 and Day 8 (21-day cycle). Control Arm: Recommended doses and schedules as per package insert depending on region. Eribulin; Capecitabine; Gemcitabine; Vinorelbine Participants will be treated until disease progression as judged by local investigator review, development of unacceptable toxicity, or withdrawal of consent.

Official Title
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A Phase 3 Asian 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 Negative (HER2-) Metastatic Breast Cancer (MBC) Who Have Failed at Least 2 Prior Chemotherapy Regimens

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy
* Drug: Eribulin Mesylate Injection
* Drug: Capecitabine Oral Product
* Drug: Gemcitabine Injection
* Drug: Vinorelbine injection


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Female or male individuals aged ≥18 years at the time of signing the informed consent form Documented evidence of hormone receptor-positive HER2-negative (HR+/HER2-) MBC confirmed Refractory to or relapsed after at least 2, and no more than 4, prior systemic chemotherapy regimens for MBC Should have been previously treated with at least 1 taxane in any setting, at least 1 prior anticancer hormonal treatment in any setting Eligible for one of the chemotherapy options listed in the TPC arm Documented radiographic disease progression after the most recent therapy Measurable disease by CT or MRI in accordance with RECIST v 1.1, bone-only disease is not measurable and is not permitted. Adequate bone marrow function, hepatic and renal function 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 Individuals who have known brain metastases. Have an active second malignancy within 3 years prior to providing informed consent Individuals with active hepatitis B virus (HBV), or hepatitis C virus infection (measurable viral RNA load with polymerase chain reaction). Active serious infection requiring systemic antibiotic use within 7 days before Cycle1 Day 1. 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. Known hypersensitivity or intolerance to either of the study treatments or any of the excipients. 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 on Days 1 and 8 of a 21-day cycle. | Drug: Sacituzumab Govitecan-hziy<br>* Sacituzumab govitecan 10 mg/kg via IV injection administered on Days 1 and 8 of a 21-day cycle. Subjects will continue to receive study treatment until PD as judged by local investigator review, development of unacceptable toxicity, or withdrawal of consent.<br>* Other names: GS-0132;|
| Active Comparator: Treatment of Physician's Choice (TPC)<br>Participants will receive recommended doses and schedules as per package insert depending on region. Eribulin (1.4 mg/m^2 of eribulin mesylate or 1.23 mg/m^2 of eribulin on Days 1 and 8 of a 21-day cycle) Capecitabine (1000 to 1250 mg/m^2 twice daily on Days 1 to 14 of a 21-day cycle) Gemcitabine (800 to 1200 mg/m^2 on Days 1, 8, and 15 of a 28-day cycle) Vinorelbine (25 mg/m^2 on Day 1 weekly) | Drug: Eribulin Mesylate Injection<br>* Eribulin is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.<br>* Other names: Halaven;Drug: Capecitabine Oral Product<br>* Capecitabine is administered orally (PO) following recommended doses and regimens as per approved package inserts.<br>* Other names: Xeloda;Drug: Gemcitabine Injection<br>* Gemcitabine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.<br>* Other names: Gemzar;Drug: Vinorelbine injection<br>* Vinorelbine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.<br>* Other names: Navelbine;|

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 from the date of randomization until the date of disease progression (PD) or death, whichever occurs earlier. Disease progression will be determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) by Independent Reviewing Committee (IRC). | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as from the date of randomization to death from any cause. | Up to 4 years | 
| Objective Response Rate (ORR) by IRC | ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR). | Up to 4 years | 
| Duration of Response (DOR) by IRC | DOR is defined as from the date of first onset of tumor response (CR or PR) to PD or death, whichever occurs earlier. | Up to 4 years | 
| Clinical Benefit Rate (CBR) by IRC | CBR is defined as best overall response of CR or PR or durable stable disease (SD) (duration of SD ≥ 6 months after randomization). | Up to 4 years | 
| Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 |  | First dose date up to 4 years plus 30 days | 
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) According to NCI CTCAE Version 5.0 |  | First dose date up to 4 years plus 30 days | 
| Change From Baseline of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30, Version 3.0 (EORTC QLQ-C30) Score | The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) to assess 15 scales; 1 global health status/quality of life (QOL), 5 functional scales (physical, role, cognitive, emotional, and social), and 9 symptom/item scales(fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of function, a high score for the global health status/QOL represents a high QOL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. | Baseline, up to 4 years | 
| Change From Baseline of the European Quality of Life 5-Dimensions 5 Levels Instrument (EuroQOL EQ-5D-5L) Score | The EQ-5D-5L is an instrument for use as a measure of health outcome.The EQ-5D-5L consists of 2 sections: the EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ-VAS indicate better health. | Baseline, up to 4 years | 
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) | NCI PRO-CTCAE is a patient-reported item library used to evaluate symptomatic treatment-emergent adverse events in participants on cancer clinical trials. The items selected for this study include: decreased appetite, nausea, vomiting, constipation, diarrhea, abdominal pain, shortness of breath, hair loss, and fatigue. | Baseline, up to 4 years | 
| Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy and Free SN-38 | Cmax is defined as the maximum observed concentration of drug. | Up to 4 years | 
| PK Parameter: Tmax of of Sacituzumab Govitecan-hziy and Free SN-38 | Tmax is defined as the time to maximum drug concentration. | Up to 4 years | 
| PK Parameter: Ctrough of Sacituzumab Govitecan-hziy and Free SN-38 | Ctrough is defined as the concentration of drug at the end of the dosing interval. | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sacituzumab govitecan, IMMU-132, Unresectable or Metastatic Breast Cancer, hormonal receptor, HR positive, Anti-TROP2, Human epidermal growth factor receptor 2 (HER2) Negative, Antibody Drug Conjugate