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)

Gilead Sciences

Status and phase: Enrolling; Phase 3

Conditions: Triple Negative Breast Cancer

Treatments: Drug: Capecitabine; Drug: Sacituzumab govitecan-hziy (SG); Drug: Pembrolizumab

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT05633654

GS-US-595-6184

2024-512279-10 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,514 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,514 participants in 2 patient groups

Sacituzumab govitecan-hziy (SG) + Pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Sacituzumab govitecan-hziy (SG)

Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine

Active Comparator group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Capecitabine