Study of Sacituzumab Govitecan-hziy plus Pembrolizumab Versus Treatment of Physician's Choice Plus Pembrolizumab in Participants with Previously Untreated, Locally Advanced, Inoperable (cannot be removed surgically), or Metastatic (spread to other locations in the body) Triple Negative Breast Cancer (breast cancer that does not have receptors for Oestrogen and progesterone hormones or HER2 proteins) that express PD-L1 biomarker (a type of protein found on cancer cells).
- Conditions
- Programmed cell death ligand 1 (PD-L1) positive metastatic triple-negative breast cancerMedDRA version: 27.0Level: LLTClassification code 10084066Term: Triple negative breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005742-14-AT
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 440
Patients must meet all of the following inclusion criteria to be eligible for participation in this study (no waivers for patient eligibility will be offered or permitted):
1) Female or male patients, regardless of race and/or ethnic group, who are18 years of age or older, able to understand and give written informed consent
2) Patients 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.
3) Have provided representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in blocks (preferably) or have at least 20 to 25 freshly sectioned unstained slides from fresh biopsy tissue (preferred) or archival tissue block for central testing of ER, progesterone receptor, HER2, PD-L1, Trop-2, and additional biomarker testing. A baseline biopsy is required if archival tissue is not available and this procedure must be performed prior to the first dose of study treatment and after the patient provides written informed consent. Fine needle aspirates and bone biopsies are not suitable samples.
Note: Tumor tissue quality must be confirmed by the central laboratory. Submission of another tumor specimen may be required if provided specimen is not adequate for assessment. A discussion with the medical monitor is required if only 15 to 19 unstained slides are available and it is not clinically feasible to obtain a new biopsy.
4) ECOG performance status score of 0 or 1 (Appendix 11.6).
5) Life expectancy = 3 months.
6) Recovered from major surgery for = 2 weeks.
7) Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study treatment initiations (hemoglobin = 9 g/dL, ANC = 1500/mm3, and platelets = 100,000/µL).
8) Adequate hepatic function (bilirubin = 1.5 × ULN, AST and ALT = 2.5 × ULN or = 5 × ULN if known liver metastases, and serum albumin > 3 g/dL).
9) Creatinine clearance = 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft 1976}.
10) International normalized ratio (INR)/PT and PTT or aPTT = 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy.
11) Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in the protocol Appendix 11.4.
12) Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 348
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 92
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) 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.
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.
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 posttreatment 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, 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 Class III or greater congestive heart failure or known left ventricular ejection fraction of < 40%.
12) Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrollment.
13) Have active serious infection requiring systemic antimicrobial therapy.
14) Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
15) Have active HBV (defined as having a positive HBsAg test) or HCV.
16) Have other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
17) Has a diagnosis of immunodeficie
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method