Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/NSABP B-63)

• ClinicalTrials.gov Identifier: NCT05633654
• Recruitment Status: Recruiting
• First Posted: December 1, 2022
• Last Update Posted: May 1, 2024
• Sponsor: Gilead Sciences
• Collaborators: Alliance Foundation Trials, LLC.; NSABP Foundation Inc
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: November 21, 2022
• First Posted Date: December 1, 2022
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: December 12, 2022
• Estimated Primary Completion Date: June 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2022)

Invasive Disease-free Survival (iDFS) [ Time Frame: Up to 60 months ]

iDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence, invasive contralateral breast cancer.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 20, 2023)

• Overall Survival (OS) [ Time Frame: Up to 96 months ]
  OS is defined as the time from the date of randomization until death due to any cause.
• Distant Disease-free Survival (dDFS) [ Time Frame: Up to 60 months ]
  dDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): distant recurrence, or second primary invasive cancer.
• Recurrence-free Survival (RFS) [ Time Frame: Up to 60 months ]
  RFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to 38 months plus 30 days ]
• Percentage of Participants Experiencing Laboratory Abnormalities [ Time Frame: First dose date up to 38 months plus 30 days ]
• Time to Worsening (TTW) of Quality of Life (QoL) Based on Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) Trial Outcome Index (TOI) Scores [ Time Frame: Up to 60 months ]
  TTW of FACT-B TOI scores will be analyzed for each index, the TTW of FACT-B scores will be measured from the randomization date and to the time the participants first experienced a first score of worsening.

Original Secondary Outcome Measures (submitted: November 21, 2022)

• Overall Survival (OS) [ Time Frame: Up to 96 months ]
  OS is defined as the time from the date of randomization until death due to any cause.
• Distant Disease-free Survival (dDFS) [ Time Frame: Up to 60 months ]
  dDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): distant recurrence, or second primary invasive cancer.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to 38 months plus 30 days ]
• Percentage of Participants Experiencing Laboratory Abnormalities [ Time Frame: First dose date up to 38 months plus 30 days ]
• Time to Worsening (TTW) of Quality of Life (QoL) Based on Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) Trial Outcome Index (TOI) Scores [ Time Frame: Up to 60 months ]
  TTW of FACT-B TOI scores will be analyzed for each index, the TTW of FACT-B scores will be measured from the randomization date and to the time the participants first experienced a first score of worsening.

• 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 in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/NSABP B-63)
• Official Title: A Randomized, Open-label, Phase 3 Study of Adjuvant Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy
• Brief Summary: The goal of this study is to find out if the experimental product, sacituzumab govitecan-hziy (SG) in combination with pembrolizumab given after surgery, is effective and safe compared to the treatment of physician's choice (TPC) which includes either pembrolizumab or pembrolizumab plus capecitabine in participants with triple negative breast cancer that still remains after surgery and pre-surgical treatment.
• 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

Intervention

• Drug: Sacituzumab govitecan-hziy (SG)
  Administered intravenously
  Other Names:

  • GS-0132
  • IMMU-132
  • Trodelvy™
• Drug: Pembrolizumab
  Administered intravenously
  Other Name: KEYTRUDA®
• Drug: Capecitabine
  Tablets administered orally
  Other Name: Xeloda

Study Arms

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

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

  Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.

  Interventions:

  • Drug: Sacituzumab govitecan-hziy (SG)
  • Drug: Pembrolizumab
• Active Comparator: Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine

  Participants will receive one of the following TPC regimens determined prior to randomization:

  • Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles OR
  • Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles and capecitabine 1000 mg/m^2 orally twice daily on Days 1 through 14 of 21-day cycles for 8 cycles.

  Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.

  Interventions:

  • Drug: Pembrolizumab
  • Drug: Capecitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 21, 2022): 1514
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2031
• Estimated Primary Completion Date: June 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Age > 18 years, with residual invasive triple negative breast cancer (TNBC) in the breast or lymph nodes after neoadjuvant therapy and surgery:

  • TNBC criteria for the study is defined as estrogen receptor (ER) and progesterone receptor (PR) < 10%, human epidermal growth factor receptor 2 (HER2)-negative per American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines (immunohistochemistry (IHC) and/or in situ hybridization (ISH)).
• Adequate excision and surgical removal of all clinically evident of disease in the breast and/or lymph nodes and have adequately recovered from surgery.
• Submission of both pre-neoadjuvant treatment diagnostic biopsy and resected residual invasive disease tissue.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Individuals must have received appropriate radiotherapy and have recovered prior to starting study treatment.
• Adequate organ function.

Key Exclusion Criteria:

• Stage IV (metastatic) breast cancer as well as history of any prior (ipsi- or contralateral) invasive breast cancer.
• Prior treatment with another stimulatory or coinhibitory T-cell receptor agent (eg, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), OX-40, cluster of differentiation 137 (CD137), prior treatment with any HER2-directed agent, prior or concurrent treatment with any endocrine therapy agent.
• Evidence of recurrent disease following preoperative therapy and surgery.
• Prior treatment with topoisomerase 1 inhibitors or antibody-drug conjugates (ADCs) containing a topoisomerase inhibitor.
• Individuals with germline breast cancer gene (BRCA) mutations.
• Myocardial infarction or unstable angina pectoris within 6 months of enrollment or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias or Left ventricular ejection fraction (LVEF) of < 50%
• Active serious infections requiring anti-microbial therapy.

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: United States

Administrative Information

• NCT Number: NCT05633654
• Other Study ID Numbers: GS-US-595-6184; 2024-512279-10 ( Other Identifier: European Medicines Agency )
• 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

• Alliance Foundation Trials, LLC.
• NSABP Foundation Inc

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

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