Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) versus treatment of physician's choice (TPC) in participants with previously untreated, locally advanced, inoperable or metastatic triple-negative breast cancer whose tumors do not express programmed cell death ligand 1 (PD-L1) or in participants previously treated with anti-programmed cell death (ligand or protein) 1 (Anti-PD-(L)1) Agents in the early setting whose tumors do express PD-L1.

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 Previously Untreated, Locally Advanced, Inoperable or Metastatic Triple-Negative Breast Cancer Whose Tumors Do Not Express PD-L1 or in Patients Previously Treated With Anti-PD-(L)1 Agents in the Early Setting Whose Tumors Do Express PD-L1

Conditions
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Triple Negative Breast Cancer, PD-L1 Negative

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy
* Drug: Paclitaxel
* Drug: nab-Paclitaxel
* Drug: Gemcitabine
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Individuals, regardless of race and ethnic group, with previously untreated locally advanced, inoperable or metastatic triple-negative breast cancer (TNBC) Individuals whose tumors are programmed cell death ligand 1 (PD-L1) negative at screening or individuals whose tumors are PD-L1 positive at screening if they have received an anti-PD-(L)1 inhibitor in the (neo) adjuvant setting or if they cannot be treated with a checkpoint inhibitor due to a comorbidity Centrally confirmed TNBC and PD-L1 status on fresh or archival tissue Individuals must have completed treatment for Stage I-III breast cancer, if indicated, and ≥ 6 months must have elapsed (with the exception of endocrine therapy) between completion of treatment with curative intent and first documented local or distant disease recurrence Individuals presenting with de novo metastatic TNBC are eligible Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) in accordance with per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. as evaluated locally Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 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 Individuals with human immunodeficiency virus (HIV) must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease Key Exclusion Criteria: Positive serum pregnancy test or women who are lactating Received systemic anticancer treatment within the previous 6 months or radiation therapy within 2 weeks prior to enrollment Have not recovered from adverse events (AEs) due to a previously administered agent at the time study entry May not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Individuals participating in observational studies are eligible Previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor Active second malignancy Active serious infection requiring antibiotics Positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 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 10 mg/kg on Days 1 and 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 1 of the 3 allowed regimens: Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of a 28-day cycle Nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of a 28-day cycle Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of a 21-day cycle | Drug: Paclitaxel<br>* Administered intravenously<br>Drug: nab-Paclitaxel<br>* Administered intravenously<br>* Other names: Abraxane®;Drug: Gemcitabine<br>* Administered intravenously<br>Drug: Carboplatin<br>* Administered intravenously<br>|

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 (RECIST) Version 1.1 | PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD), or death (whichever comes first). | Randomization up to approximately 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from the date of randomization until death due to any cause. | Randomization up to approximately 57 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. | Randomization up to approximately 57 months | 
| Duration of Response (DOR) as Assessed by BICR 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 definitive PD or death from any cause (whichever comes first). | Randomization up to approximately 57 months | 
| Time to Response (TTR) as Assessed by BICR per RECIST Version 1.1 | TTR is defined as the time from the date of randomization until the first documentation of CR or PR. | Randomization up to approximately 57 months | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | First dose date up to approximately 57 months plus 30 days | 
| Percentage of Participants Experiencing Clinical Laboratory Abnormalities |  | First dose date up to approximately 57 months plus 30 days | 
| Change from Baseline in the Physical Functioning Domain as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, 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) 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. | Randomization up to approximately 57 months | 
| Time to Deterioration (TTD) of Fatigue Scale of the EORTC QLQ-C30 | TTD is defined as the time between the date of randomization and the date of assessment at which a patient experienced a deterioration (≥ 10 points deterioration from baseline in the fatigue scale) or death. | Randomization up to approximately 57 months |