A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer, Whose Tumors Express PD-L1
- Conditions
- Breast cancerTriple-Negative Breast Cancer10006291
- Registration Number
- NL-OMON51425
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 18
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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- PFS is defined as the time from the date of randomization until the date of<br /><br>objective progressive disease (PD), as assessed by BICR per Response Evaluation<br /><br>Criteria in Solid Tumors (RECIST) Version 1.1, or death (whichever comes<br /><br>first).</p><br>
- Secondary Outcome Measures
Name Time Method