Breast cancer Triple-Negative Breast Cancer
Conditions
Interventions
Please refer to Tables 1-3 in the Main ICF.
Sponsors
Gilead Sciences
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Eligible participants include adults age >=18 years with locally advanced inoperable or metastatic TNBC who have not received previous systemic therapy for advanced disease and whose tumors are PD-L1 positive at screening. Participants must have completed systemic treatment for Stage I to III breast cancer, if indicated, and >=6months must have elapsed between completion of treatment with curative intent and first documented local or distant disease recurrence. Participants presenting with de novo metastatic TNBC are eligible for this study. Tumors will be centrally confirmed for TNBC and PD-L1 status. Triple-negative breast cancer will be defined as negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2; immunohistochemistry [IHC] 0, IHC 1+ or IHC 2+/in situ hybridization [ISH]) as per current American Society of Clinical Oncology or College of American Pathologists guidelines {Allison 2020, Wolff 2018}. Tumor PD-L1 status will be assessed using the PD-L1 IHC 22C3 assay and participants with tumors with a CPS>=10 will be eligible. Additionally, eligible participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and life expectancy of >=3months.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following exclusion criteria are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted): 1) Positive serum pregnancy test (Appendix 11.4) or women who are lactating. 2) Known or severe (>= Grade 3) hypersensitivity or allergy to SG, pembrolizumab, and/or the chemotherapy regimen of choice in the TPC arm (eg, nab-paclitaxel, paclitaxel, gemcitabine, or carboplatin), their metabolites, or formulation excipient. 3) Have received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) 4) Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.6.1. 5) Patients may not have received systemic anticancer treatment(with the exception of endocrine therapy) within the previous 6 months or radiation therapy within 2 weeks prior to enrollment. Patients must have recovered from AEs due to a previously administered agent to <= Grade 1 or baseline at the time of study entry. * Note: patients with <= Grade 2 neuropathy or any grade alopecia are an exception to this criterion and will qualify for the study. Patients with endocrine-related AEs Grade <=2 requiring treatment or hormone replacement may be eligible. * Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 6) Patients may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Patients participating in observational studies are eligible. 7) Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor. 8) Have an active second malignancy. Note: patients with a history of malignancy that has been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll. 9) Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate (with the exception of those treated with chemotherapy) provided they have stable CNS disease (defined as radiographic stability demonstrated with a minimum of 2 post-treatment brain imaging assessments; one performed during screening) for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and have also been clinically stable for at least 2 weeks while taking <= 10 mg/day of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability. 10) Have undergone an allogenic tissue or solid organ transplant. 11) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death (whichever comes first). | — |
Secondary
| Measure | Time frame |
|---|---|
| * OS is defined as the time from the date of randomization until death due to any cause. * ORR is defined as the proportion of patients who achieve complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response as assessed by BICR per RECIST Version 1.1. * DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of objective PD or death from any cause (whichever comes first) as assessed by BICR per RECIST Version 1.1 * TTR is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR per RECIST Version 1.1 * Incidence of treatment-emergent AEs (TEAEs) and clinical laboratory abnormalities. * TTD of physical functioning domain of the EORTC QLQ-C30 * TTD of role functioning, global health status/QOL, pain, and fatigue subscale domains of the EORTC QLQ-C30 Exploratory Endpoints: * Correlation of clinical outcome (PFS, OS, ORR, and DOR) with baseline tumor Trop-2 expression * Correlation of clinical outcome (PFS, OS, ORR, and DOR) with tumor, tumor microenvironment, and blood biomarkers at baseline and after SG plus pembrolizumab treatment * Clearance of circulating tumor DNA upon SG plus pembrolizumab treatment * Correlation of AEs to UGT1A1 status * Correlation of PK and immunogenicity of SG * Additional QOL endpoints include mean change from baseline, TTD (in addition to the subscales specified as secondary endpoints), time to improvement, proportion improved, and proportion worsened | — |
Countries
Netherlands
Outcome results
None listed