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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Sacituzumab govitecan-hziy (SG)
* Drug: Pembrolizumab
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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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. 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.

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) + Pembrolizumab<br>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. | Drug: Sacituzumab govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: Trodelvy™;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;|
| Active Comparator: Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine<br>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. | Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;Drug: Capecitabine<br>* Tablets administered orally<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease-free Survival (iDFS) | 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. | Up to 60 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. | Up to 96 months | 
| Distant Disease-free Survival (dDFS) | 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. | Up to 60 months | 
| Recurrence-free Survival (RFS) | 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. | Up to 60 months | 
| 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 | 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. | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OptimICE-RD, AFT-65