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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Nov 2024 → ongoing

Decision date (initial)

2025-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2024-512279-10-00

ClinicalTrials.gov

NCT05633654

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Efficacy, Safety, Pharmacokinetic

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

Secondary objectives 5

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) QoL outcomes as measured by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) between the 2 arms

Conditions and MedDRA coding

Triple Negative Breast Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
3. 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.
4. 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%.
5. 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.
6. 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.
7. Adequate Hepatic function.

Exclusion criteria 10

1. Stage IV (metastatic) breast cancer
2. Have previously received topoisomerase 1 inhibitors or ADCs containing a topoisomerase inhibitor
3. Have received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
4. 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
5. 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.
6. Concurrent serious uncontrolled infections requiring treatment
7. History of any prior (ipsi- or contralateral) invasive breast cancer. Note: Prior DCIS is allowed.
8. Patients with germline BRCA mutations
9. Evidence of recurrent disease (locoregional and/or distant relapse) following preoperative therapy and surgery
10. Inadequate cardiac function postoperatively, ie, screening LVEF < 50% on ECHO or MUGA

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 5

1. OS is defined as the time from the date of randomization until death due to any cause.
2. 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.
3. 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
4. Incidence of TEAEs and clinical laboratory abnormalities
5. TTW of QoL based on FACT-B Trial Outcome Index (TOI) score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 7

Locations

6 EU/EEA countries · 135 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 199 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications