ASCENT-05: 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

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05633654

Collaborator

Alliance Foundation Trials, LLC. (Other)

1,514

Enrollment

Locations

Arms

96.7

Anticipated Duration (Months)

189.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer	Biological: Sacituzumab govitecan-hziy (SG) Biological: Pembrolizumab Drug: Capecitabine	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1514 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 12, 2022

Anticipated Primary Completion Date :

Jul 1, 2027

Anticipated Study Completion Date :

Jan 1, 2031

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: Sacituzumab govitecan-hziy (SG) Administered intravenously Other Names: GS-0132 IMMU-132 Trodelvy™ Biological: Pembrolizumab Administered intravenously Other Names: Keytruda®
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.	Biological: Pembrolizumab Administered intravenously Other Names: Keytruda® Drug: Capecitabine Tablets administered orally Other Names: Xeloda

Arm

Intervention/Treatment

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.

Biological: Sacituzumab govitecan-hziy (SG)

Administered intravenously

Other Names:

GS-0132

IMMU-132

Trodelvy™

Biological: Pembrolizumab

Administered intravenously

Other Names:

Keytruda®

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.

Biological: Pembrolizumab

Administered intravenously

Other Names:

Keytruda®

Drug: Capecitabine

Tablets administered orally

Other Names:

Xeloda

Outcome Measures

Primary Outcome Measures

Invasive Disease-free Survival (iDFS) [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.

Secondary Outcome Measures

Overall Survival (OS) [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) [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) [First dose date up to 38 months plus 30 days]
Percentage of Participants Experiencing Laboratory Abnormalities [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (IHC and/or 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.
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 known 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Palo Verde Hematology Oncology	Glendale	Arizona	United States	85304
2	Los Angeles Cancer Network	Los Angeles	California	United States	90017
3	Emad Ibrahim, MD, INC	Redlands	California	United States	92373
4	Piedmont Cancer Institute	Atlanta	Georgia	United States	30318
5	Regional Cancer Care Associates LLC	East Brunswick	New Jersey	United States	08816
6	Summit Medical Group, P.A.	Florham Park	New Jersey	United States	07932
7	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
8	University of Tennessee	Knoxville	Tennessee	United States	37920