This study has been transitioned to CTIS with ID 2023-504194-21-00 check the CTIS register for the current data. Primary Objective:- To compare progression-free survival (PFS) as assessed by blinded independent central review (BICR) between…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- 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 outcome
* 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
Background summary
- Sacituzumab govitecan (Trodelvy®) is currently approved by the United States
(U.S.) Food and Drug Administration (FDA) and the European
Medicines Agency*s (EMA) for previously treated advanced TNBC. It is also
approved by the U.S. FDA for the treatment of patients with bladder cancer
and cancers of the urinary tract.
- Pembrolizumab is approved by the U.S. FDA and other regulatory agencies for
the treatment of certain types of TNBC. It is also approved for the treatment
of several different types of other cancers.
The purpose of this study is to see if sacituzumab govitecan in combination
with pembrolizumab can improve lifespans of patients with advanced, PD-L1
positive TNBC and their tumor does not grow or spread when compared to
pembrolizumab in combination with chemotherapy (paclitaxel, or nab-paclitaxel,
or the combination of gemcitabine and carboplatin).
Sacituzumab govitecan will be administered at a dose of 10 mg/kg intravenously
on Days 1 and 8 of 21-day cycles, with dose modifications permitted as
specified.
Pembrolizumab will be administered at a dose of 200 mg intravenously on Day 1
of 21-day cycles, with dose modifications permitted as specified.
Study objective
This study has been transitioned to CTIS with ID 2023-504194-21-00 check the CTIS register for the current data.
Primary Objective:
- To compare progression-free survival (PFS) as assessed by blinded independent
central review (BICR) between sacituzumab govitecan (SG) and pembrolizumab
versus treatment of physician*s choice (TPC) and pembrolizumab.
Secondary Objectives:
- To compare overall survival (OS) between the 2 arms
- To compare objective response rate (ORR) as assessed by BICR between the 2
arms
- To evaluate duration of response (DOR) as assessed by BICR between the 2 arms
- To evaluate time to onset of response (TTR) as assessed by BICR between the 2
arms
- To evaluate safety and tolerability between the 2 arms
- To compare time to deterioration (TTD) in physical functioning as measured by
European Organisation for Research and Treatment of
Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [Version 3.0]) between the
2 arms
- To evaluate TTD in role functioning, global health status/quality of life
(QOL), pain, and fatigue as measured by the EORTC QLQ-C30
(Version 3.0) between the 2 arms
Exploratory Objectives:
- To assess tumor expression of trophoblast cell surface antigen-2 (Trop-2) as
a potential biomarker of response to SG plus pembrolizumab
- To explore blood and tumor biomarkers that may be associated with response to
SG plus pembrolizumab
- To explore the relationship of adverse events (AEs) to uridine diphosphate
glucuronosyltransferase 1A1 (UGT1A1) status
- To characterize the PK and immunogenicity of SG
- To evaluate additional QOL outcomes as measured by 5-level EuroQoL
(EQ-5D-5L), theEuropean Organisation for Research and Treatment of Cancer,
Breast Cancer Module (EORTC QLQ-BR23), EORTC QLQ-C30, and FACT-GP5 between the
2 arms
Study design
Study Design:
This is an international, multicenter, open-label, randomized, Phase 3 study in
participants with locally advanced inoperable or metastatic triple-negative
breast cancer (mTNBC) who have not received previous therapy for advanced
disease and whose tumors are PD-L1 positive (defined using the PD-L1 IHC 22C3
assay as tumors with a combined positive score [CPS] >= 10) at screening.
Enrolled participants may have received adjuvant or neoadjuvant chemotherapy
with or without an anti-PD-L1 or anti-PD-1 agent and/or radiotherapy in the
curative TNBC setting. However, at least 6 months must have elapsed between the
completion of systemic (neo)adjuvant breast cancer therapy or surgery
(whichever occurred last) and first local or distant recurrence. Adjuvant
radiotherapy is not included in the 6-month interval, but patients must not
have received radiotherapy treatment within 2 weeks prior to randomization.
Participants with brain metastases who have been treated and are
radiographically stable for at least 4 weeks are eligible if they have also
been clinically stable for at least 2 weeks on a prednisone equivalent dose of
<= 10 mg daily.
Participants meeting eligibility will be randomly assigned (1:1) to one of 2
arms:
- Arm A: SG 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles and
pembrolizumab 200 mg on Day 1 of 21-day cycles. Pembrolizumab will be
administered for a maximum of 35 cycles (approximately 2 years).
- Arm B: TPC; 21 or 28-day cycles and pembrolizumab 200 mg on Day 1 of 21-day
cycles. Pembrolizumab will be administered for a maximum of 35 cycles
(approximately 2 years). The TPC will be limited to one of the following
treatment regimens:
- Gemcitabine 1000 mg/m2 with carboplatin area under the curve (AUC) 2
intravenously on Days 1 and 8 of 21-day cycles
- Paclitaxel 90 mg/m2 intravenously on Days 1, 8, and 15 of 28-day cycles
- nab-Paclitaxel 100 mg/m2 intravenously on Days 1, 8, and 15 of 28-day cycles
No other treatment regimen is permitted and no combination or crossovers of the
3 choices are permitted. Treatment will be administered until BICR-verified
disease progression, unacceptable toxicity, consent withdrawal, or death.If
institutional dose and regimen guidelines
differ, the site may utilize institutional guidelines if approved by the
sponsor or designee.
Randomized participants will be stratified by the following factors:
- De novo versus recurrent disease within 6 to 12 months from completion of
treatment in the curative setting versus recurrent disease occurring > 12
months from completion of treatment in the curative setting
- Curative treatment interval is defined as the time between completion of
systemic (neo)adjuvant breast cancer therapy or surgery (whichever occurred
last) and first local or distant recurrence; adjuvant radiotherapy is not
included in the 6-month interval
- Geographic region (US/Canada/Western Europe versus rest of world)
- Prior exposure to anti-PD-1 or anti-PD-L1 agent (yes or no)
Tumor assessments will be obtained by computed tomography (CT) or magnetic
resonance imaging (MRI) scans every 8 weeks during the first 18 months and then
every 12 weeks thereafter until BICR-verified progression of disease or
initiation of any new anticancer therapy. Bone scans may be conducted as
clinically indicated. For each participant, the same imaging modality should be
used throughout the study.
Images will be evaluated for tumor status by a BICR committee and assessment by
a central imaging vendor as per RECIST Version 1.1. Complete responses (CR) and
partial response (PR) will be confirmed by a follow-up scan at least 4 weeks
from the date the response was first documented. Additional CT or MRI scans may
be performed at the discretion of the treating physician to assess disease
status as medically indicated. Scans will be collected for review by the BICR.
In case of progression on clinical grounds, the investigator will make every
effort to document progression radiographically for review by the BICR.
An end of treatment (EOT) visit will be conducted within 30 days (± 7 days)
after the last dose of study treatment. Following BICR-verified radiographic
progression and study treatment discontinuation, participants who were
randomized to the control arm (pembrolizumab + TPC
chemotherapy) may be eligible to receive SG in the crossover phase of this
study. Participants who discontinue study treatment without BICR-verified
progression should be followed for disease status with imaging studies per
protocol until verification of progression or start of new anticancer therapy,
whichever occurs first. All patients, including those who prematurely terminate
study treatment, will be followed every 12 weeks (± 7 days) or more frequently
for survival until death or withdrawal of consent.
Participants will undergo screening, tumor, safety, laboratory, biomarker, PK,
immunogenicity and QOL evaluations.
Intervention
Please refer to Tables 1-3 in the Main ICF.
Study burden and risks
Please refer to section E9 of this request form.
Lakeside Drive 333
Foster City CA 94404
US
Lakeside Drive 333
Foster City CA 94404
US
Listed location countries
Age
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
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, 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.
a) For patients with a history of HBV infection, a hepatitis B core antibody
test should be
conducted at screening. If positive, hepatitis B DNA testing will be performed
and if active
HBV infection is ruled out, the patient may be eligible.
b) Patients who are HCV antibody positive with undetectable HCV viral load may
be eligible.
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 immunodeficiency or receiving systemic corticosteroid
therapy (higher
than physiologic doses) >= 10 mg of prednisone per day or equivalent] or any
other form of
immunosuppressive therapy within 14 days prior to randomization.
18) Has received a live or live-attenuated vaccine within 30 days prior to
randomization.
Administration of killed vaccines are allowed.
19) Has an active autoimmune disease that has required systemic treatment in
the past 2 years
(eg, with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid
replacement therapy
for adrenal or pituitary insufficiency) is not considered a form of systemic
treatment and is
allowed.
20) Has a history of (noninfectious) pneumonitis/interstitial lung disease that
required steroids or
has current pneumonitis/interstitial lung disease.
21) Has received prior radiotherapy within 2 weeks of start of study
intervention. Patients must
have recovered from all radiation-related toxicities, not require
corticosteroids, and not have
had radiation pneumonitis. A 1-week washout is permitted for palliative
radiation (2 weeks
of radiotherapy) to non-CNS disease.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-504194-21-00 |
| EudraCT | EUCTR2021-005742-14-NL |
| CCMO | NL81639.028.22 |