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

Phase 3

Recruiting

Conditions: Triple Negative Breast Cancer

Registration Number: 2024-512279-10-00

Lead Sponsor: Gilead Sciences Inc.

Brief Summary: To compare invasive disease-free survival (iDFS) between SG and pembrolizumab versus TPC

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Female

Target Recruitment: 632

Inclusion Criteria

Assigned male or female at birth 18 years of age or older (or minimum age according to country-specific requirements), able to understand and give written informed consent

Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Patients must have a history of clinical stage T1, N1-2 or T2-4, N0-2 and histologically confirmed TNBC as determined by the investigator with residual invasive disease in the breast or lymph node(s) after completion of neoadjuvant therapy and surgery. Additionally, the presence of distant metastatic disease must be ruled out. TNBC criteria for the study is defined as ER and PgR ≤10%, HER2-negative per ASCO/CAP guidelines (IHC and/or ISH) TNBC confirmation from posttreatment surgical tissue is preferred if possible . In the case of discordant expression results, eligibility must be discussed and determined on a case-by-case basis with the sponsor medical monitor. Staging should be done according to the primary tumor-regional lymph node anatomic staging criteria of the American Joint Committee on Cancer, eighth edition. In the case of known local progression during neoadjuvant therapy, distant metastases must be excluded by adequate imaging (computed tomography [CT]/magnetic resonance imaging [MRI] recommended) prior to study entry.

Patients must have received neoadjuvant chemotherapy (taxane and/or anthracycline-based regimen) with or without an aPD-(L)1 or platinum agent for a minimum of 6 cycles or 18 weeks prior to surgery. Note: For patients who have received pembrolizumab in the neoadjuvant setting, up to 3 cycles of adjuvant pembrolizumab 200 mg Q3W administered with or without radiotherapy is allowed prior to study entry. Note: Enrollment of patients who have not received prior neoadjuvant aPD-(L)1 therapy will be capped at approximately 10%.

Adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes as follows: Breast surgery: breast-conserving surgery with histologically negative margins of excision or total mastectomy with no gross residual disease at the margin of resection, and ideally, should be histologically negative as well. For patients who underwent breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection. If invasive disease is present in both breasts, participation in the study is permitted as long as the other eligibility criteria are met. Lymph node surgery: In case of positive results from a fine-needle aspiration, core biopsy, or sentinel node biopsy performed prior to preoperative therapy, additional surgical evaluation of the axilla following preoperative therapy should have been performed (eg, sentinel node evaluation, targeted axillary dissection, and or axillary lymph node dissection [ALND]). If sentinel node biopsy performed before preoperative therapy was negative, no additional surgery evaluation of the axilla is required after preoperative therapy. If the only sentinel node identified by isotope scan is in the internal mammary chain, surgical evaluation of the axilla is recommended. If sentinel node biopsy performed after preoperative therapy is positive with macrometastases, ALND is required. In the presence of micrometastases, ALND is recommended unless not clinically feasible or not aligned with local/institutional practice. If sentinel node evaluation after preoperative therapy is negative, no further additional surgical evaluation of the axilla is required. Axillary dissection without sentinel node evaluation is permitted as the initial or sole axillary evaluation after preoperative therapy. The presence of micrometastases in lymph nodes after preoperative therapy counts as residual invasive disease, whereas the presence of isolated tumor cells (ITCs) does not. If patients have ITCs in the setting of residual breast disease, nodal irradiation is recommended.

Patients must have received appropriate radiotherapy and have recovered prior to starting study treatment. At a minimum radiotherapy is required for the following: Breast-conserving surgery: whole breast radiation is required. Regional node radiation is required if the patient presented with cT3-4 or cN2 disease at initial diagnosis. Total mastectomy: chest wall and regional node radiation is required if the patient presented with cT3-4 or cN2 disease at initial diagnosis.

Adequate Hepatic function.

Exclusion Criteria

Stage IV (metastatic) breast cancer

Inadequate cardiac function postoperatively, ie, screening LVEF < 50% on ECHO or MUGA

Have previously received topoisomerase 1 inhibitors or ADCs containing a topoisomerase inhibitor

Have received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).

Met any of the following criteria for cardiac disease: a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment. b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation c) New York Heart Association (NYHA) Class III or greater congestive heart failure

Prior neoadjuvant HER2-directed therapy; prior endocrine therapy for > 4 weeks or planned concurrent endocrine therapy while receiving on-study treatment. ■ Endocrine therapy for fertility preservation is an exception to this criterion. Note: For patients with hormone receptor low expression (ER or PgR ≥ 1% and ≤ 10%), endrocrine therapy is permitted per investigator’s discretion after completion of on-study treatment.

Concurrent serious uncontrolled infections requiring treatment

History of any prior (ipsi- or contralateral) invasive breast cancer. Note: Prior DCIS is allowed.

Patients with germline BRCA mutations

Evidence of recurrent disease (locoregional and/or distant relapse) following preoperative therapy and surgery

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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, or invasive contralateral breast cancer.		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, or invasive contralateral breast cancer.

Secondary Outcome Measures

Name	Time	Method
OS is defined as the time from the date of randomization until death due to any cause.		OS is defined as the time from the date of randomization until death due to any cause.
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.		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.
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		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
Incidence of TEAEs and clinical laboratory abnormalities		Incidence of TEAEs and clinical laboratory abnormalities
TTW of QoL based on FACT-B Trial Outcome Index (TOI) score		TTW of QoL based on FACT-B Trial Outcome Index (TOI) score

Trial Locations

Locations (103): Klinikum Esslingen GmbH
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Esslingen Am Neckar, Germany
Marienhospital Bottrop gGmbH
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Bottrop, Germany
St. Josefs-Hospital Wiesbaden GmbH
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Wiesbaden, Germany
Kath. St. Paulus GmbH
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Dortmund, Germany
MVZ fuer Haematologie und Onkologie Ravensburg GmbH
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Ravensburg, Germany
Technische Universitaet Dresden
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Dresden, Germany
SRH Wald-Klinikum Gera GmbH
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Gera, Germany
Rotkreuzklinikum Muenchen gGmbH
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Munich, Germany
HELIOS Klinikum Berlin-Buch GmbH
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Berlin, Germany
Haematologie-Onkologie im Zentrum MVZ GmbH
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Augsburg, Germany
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Klinikum Esslingen GmbH
🇩🇪Esslingen Am Neckar, Germany
Alexander Hein
Site contact
004971131033051
a.hein.cto@klinikum-esslingen.de