Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer (ASCENT-04)

• ClinicalTrials.gov Identifier: NCT05382286
• Recruitment Status: Recruiting
• First Posted: May 19, 2022
• Last Update Posted: May 9, 2024
• Sponsor: Gilead Sciences
• Collaborator: Merck Sharp & Dohme LLC
• 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 9, 2024
• Actual Study Start Date: July 25, 2022
• Estimated Primary Completion Date: February 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 33 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: May 16, 2022)

• Overall Survival (OS) [ Time Frame: Randomization up to approximately 53 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 53 months ]
  ORR is defined as the proportion of participants who achieve 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 53 months ]
  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).
• Time to Response (TTR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Randomization up to approximately 53 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 53 months plus 30 days ]
• Percentage of Participants Experiencing Clinical Laboratory Abnormalities [ Time Frame: First dose date up to 53 months plus 30 days ]
• Time to Deterioration (TTD) in Global Health Status/Quality of Life (QoL) Scale 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 53 months ]
  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).
• TTD of Pain Score as Measured by EORTC QLQ-C30 [ Time Frame: Randomization up to approximately 53 months ]
  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).
• TTD of Fatigue Score as Measured by EORTC QLQ-C30 [ Time Frame: Randomization up to approximately 53 months ]
  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 (ie, a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the participant).
• TTD of Physical Functioning Domain Score as Measured by EORTC QLQ-C30 [ Time Frame: Randomization up to approximately 53 months ]
  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 (ie, a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the participant).
• TTD of Role Functioning Score as Measured by EORTC QLQ-C30 [ Time Frame: Randomization up to approximately 53 months ]
  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 (ie, a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the participant).

• Original Secondary Outcome Measures: Same as current
• 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 and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab 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 and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer, Whose Tumors Express PD-L1
• Brief Summary: The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) and pembrolizumab versus treatment of physician's choice (TPC) and pembrolizumab in participants with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer, whose tumors express programmed cell death ligand 1 (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 Positive

Intervention

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

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

Study Arms

• Experimental: Sacituzumab Govitecan-hziy (SG) + Pembrolizumab

  Participants will receive SG 10 mg/kg on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg on Day 1 of 21-day cycles

  Pembrolizumab will be administered for a maximum of 35 cycles.

  Interventions:

  • Drug: Sacituzumab Govitecan-hziy
  • Drug: Pembrolizumab
• Active Comparator: Pembrolizumab + Treatment of Physician's Choice (TPC)

  Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens:

  • Paclitaxel 90 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
  • nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of 28-day cycles
  • Gemcitabine 1000 mg/m^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 16, 2022): 440
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2027
• Estimated Primary Completion Date: February 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Individuals with locally advanced, inoperable, or metastatic triple-negative breast cancer (TNBC) who have not received previous systemic therapy for advanced disease and whose tumors are programmed cell death ligand 1 (PD-L1) positive at screening.

  • Individuals must have completed treatment for Stage I to III breast cancer, if indicated, and ≥ 6 months must have elapsed between completion of treatment with curative intent and first documented local or distant disease recurrence.
  • Individuals presenting with de novo metastatic TNBC are eligible for this study.
  • TNBC status and tumor PD-L1 combined positive score (CPS) will be confirmed centrally on a recent or archival tumor specimen.
  • Individuals must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria as evaluated locally.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Demonstrates adequate organ function
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
• Individuals with 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 prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor.
• Individuals may not have received systemic anticancer treatment (with the exception of endocrine therapy) within the previous 6 months or radiation therapy within 2 weeks prior to enrollment.
• Individuals 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.
• Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.
• Have an active second malignancy.
• Have active serious infection requiring antibiotics.
• Individuals positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.

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, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Puerto Rico, Singapore, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05382286
• Other Study ID Numbers: GS-US-592-6173; 2021-005742-14 ( EudraCT Number ); KEYNOTE-D19 ( Other Identifier: Merck Sharp & Dohme LLC ); jRCT2041220123 ( Registry Identifier: Japan Registry of Clinical Trials ); MK-3475-D19 ( Other Identifier: Merck Sharp & Dohme LLC )
• 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: Merck Sharp & Dohme LLC

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

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