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 (ASCENT-03)

• ClinicalTrials.gov Identifier: NCT05382299
• Recruitment Status: Recruiting
• First Posted: May 19, 2022
• Last Update Posted: May 3, 2024
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: May 16, 2022
• First Posted Date: May 19, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: July 20, 2022
• Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2022)

Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Randomization up to approximately 22 months ]

PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD), or death (whichever comes first).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 19, 2023)

• Overall Survival (OS) [ Time Frame: Randomization up to approximately 57 months ]
  OS is defined as the time from the date of randomization until death due to any cause.
• Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 57 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.
• Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 57 months ]
  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).
• Time to Response (TTR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 57 months ]
  TTR is defined as the time from the date of randomization until the first documentation of CR or PR.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to approximately 57 months plus 30 days ]
• Percentage of Participants Experiencing Clinical Laboratory Abnormalities [ Time Frame: 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). [ Time Frame: Randomization up to approximately 57 months ]
  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.
• Time to Deterioration (TTD) of Fatigue Scale of the EORTC QLQ-C30 [ Time Frame: Randomization up to approximately 57 months ]
  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.

Original Secondary Outcome Measures (submitted: May 16, 2022)

• Overall Survival (OS) [ Time Frame: Randomization up to approximately 57 months ]
  OS is defined as the time from the date of randomization until death due to any cause.
• Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 57 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.
• Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 57 months ]
  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).
• Time to Response (TTR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 57 months ]
  TTR is defined as the time from the date of randomization until the first documentation of CR or PR.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to approximately 57 months plus 30 days ]
• Percentage of Participants Experiencing Clinical Laboratory Abnormalities [ Time Frame: 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) [ Time Frame: Randomization up to approximately 57 months ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Triple Negative Breast Cancer
• PD-L1 Negative

Intervention

• Drug: Sacituzumab Govitecan-hziy
  Administered intravenously
  Other Names:

  • IMMU-132
  • Trodelvy™
  • GS-0132
• Drug: Paclitaxel
  Administered intravenously
• Drug: nab-Paclitaxel
  Administered intravenously
  Other Name: Abraxane®
• Drug: Gemcitabine
  Administered intravenously
• Drug: Carboplatin
  Administered intravenously

Study Arms

• Experimental: Sacituzumab Govitecan-hziy (SG)
  Participants will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle.
  Intervention: Drug: Sacituzumab Govitecan-hziy
• Active Comparator: Treatment of Physician's Choice (TPC)

  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
  Interventions:

  • Drug: Paclitaxel
  • Drug: nab-Paclitaxel
  • Drug: Gemcitabine
  • Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 16, 2022): 540
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2027
• Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Puerto Rico, Romania, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05382299
• Other Study ID Numbers: GS-US-592-6238; 2021-005743-79 ( EudraCT Number ); DOH-27082022-7958 ( Registry Identifier: South African National Clinical Trials Registry ); jRCT2041220122 ( Registry Identifier: Japan Registry of Clinical Trials ); CTR20234162 ( Registry Identifier: China: Drug Clinical Trial Registration and Information Disclosure Platform )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: May 2024