Title
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 ASCENT-05 / OptimICE-RD

Description
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.

Objective
Primary Objective:
1. To compare invasive disease-free survival (iDFS) between sacituzumab govitecan (SG) and pembrolizumab versus treatment of physician s choice (TPC).

Secondary Objectives:
1. To compare overall survival (OS) between the 2 arms.
2. To compare distant disease-free survival (dDFS) as assessed by investigator between the 2 arms.
3. To compare recurrence-free survival (RFS) as assessed by investigator between the 2 arms.
4. To compare safety and tolerability between the 2 arms.
5. To compare time to worsening (TTW) quality of life (QoL) outcomes as measured by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) between the 2 arms.

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

Key Eligibility 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.

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.

Applicable Disease Sites
Breast

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital