Trial Title:
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan Versus Sacituzumab Govitecan Alone in the Treatment of Advanced Urothelial Cancer
NCT ID:
NCT06524544
Condition:
Locally Advanced Urothelial Carcinoma
Metastatic Urothelial Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Pembrolizumab
Camptothecin
Irinotecan
Immunoconjugates
Sacituzumab govitecan
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (sacituzumab govitecan)
Arm group label:
Arm II (pembrolizumab, sacituzumab govitecan)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm I (sacituzumab govitecan)
Arm group label:
Arm II (pembrolizumab, sacituzumab govitecan)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm I (sacituzumab govitecan)
Arm group label:
Arm II (pembrolizumab, sacituzumab govitecan)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Arm II (pembrolizumab, sacituzumab govitecan)
Other name:
BCD-201
Other name:
GME 751
Other name:
GME751
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK 3475
Other name:
MK-3475
Other name:
MK3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
Pembrolizumab Biosimilar GME751
Other name:
Pembrolizumab Biosimilar QL2107
Other name:
QL2107
Other name:
SCH 900475
Other name:
SCH-900475
Other name:
SCH900475
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm I (sacituzumab govitecan)
Arm group label:
Arm II (pembrolizumab, sacituzumab govitecan)
Intervention type:
Biological
Intervention name:
Sacituzumab Govitecan
Description:
Given IV
Arm group label:
Arm I (sacituzumab govitecan)
Arm group label:
Arm II (pembrolizumab, sacituzumab govitecan)
Other name:
hRS7-SN38 Antibody Drug Conjugate
Other name:
IMMU 132
Other name:
IMMU-132
Other name:
IMMU132
Other name:
RS7 SN38
Other name:
RS7-SN38
Other name:
RS7SN38
Other name:
Sacituzumab Govitecan-hziy
Other name:
Trodelvy
Summary:
This phase III trial compares the effectiveness of pembrolizumab and sacituzumab
govitecan to sacituzumab govitecan alone in treating patients with urothelial cancer that
has spread to nearby tissue or lymph nodes (locally advanced) or that has spread to other
places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as
pembrolizumab, may help the body's immune system attack the cancer, and may interfere
with the ability of tumor cells to grow and spread. Sacituzumab govitecan is a monoclonal
antibody, called sacituzumab, linked to a chemotherapy drug called govitecan. Sacituzumab
attaches to TROP2 positive tumor cells in a targeted way and delivers govitecan to kill
them. Giving pembrolizumab and sacituzumab govitecan may be more effective than
sacituzumab govitecan alone in treating patients with locally advanced or metastatic
urothelial cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare overall survival (OS) between the sacituzumab govitecan monotherapy arm and
the sacituzumab govitecan + pembrolizumab arm.
SECONDARY OBJECTIVES:
I. To compare the progression free survival (PFS) between the sacituzumab govitecan
monotherapy arm and the sacituzumab govitecan + pembrolizumab arm.
II. To evaluate overall response rate (ORR) between the sacituzumab govitecan monotherapy
arm and the sacituzumab govitecan + pembrolizumab arm.
III. To evaluate clinical benefit rate (complete response [CR]/partial response [PR]
/stable disease [SD]) between the sacituzumab govitecan monotherapy arm and the
sacituzumab govitecan + pembrolizumab arm.
IV. To evaluate duration of response (DoR) between the sacituzumab govitecan monotherapy
arm and the sacituzumab govitecan + pembrolizumab arm.
V. To evaluate toxicity of the sacituzumab govitecan + pembrolizumab arm using the
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
CORRELATIVE OBJECTIVE:
I. To evaluate the potential association between tumor tissue-based, blood and
urine-based biomarkers with clinical endpoints (e.g., OS, PFS, ORR) in each arm.
EXPLORATORY OBJECTIVE:
I. To assess clinical outcomes (OS, PFS, ORR, clinical benefit rate) in prespecified
subsets based on 1) prior checkpoint inhibitor therapy response primary versus (vs.)
secondary resistance 2) prior enfortumab vedotin 3) prior platinum-based chemotherapy
(cisplatin/carboplatin) and 4) Bellmunt score / risk factors.
EXPLORATORY HEALTH RELATED QUALITY OF LIFE (HRQOL) OBJECTIVES:
I. To compare HRQOL, as assessed by the National Comprehensive Cancer Network/Functional
Assessment of Cancer Therapy Bladder Symptom Index-18 (FBISI-18) summary score between
patients on the sacituzumab govitecan arm versus the sacituzumab govitecan +
pembrolizumab arm at 6 months.
II. To compare HRQOL change from baseline, as assessed by the FBISI-18 summary score, for
patients on the sacituzumab govitecan arm versus the sacituzumab govitecan +
pembrolizumab arm at baseline, 3, 6, and 12 months.
III. To compare the change in patient-reported fatigue from baseline and across 3, 6, and
12 months as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue
(FACIT-Fatigue) summary score; change from baseline will be compared between patients on
the sacituzumab govitecan arm versus the sacituzumab govitecan + pembrolizumab arm.
IV. To compare quality-adjusted survival (overall survival x health utility score
assessed by the European Quality of Life Five Dimension Five Level [EQ-5D-5L]) between
patients on the sacituzumab govitecan arm versus the sacituzumab govitecan +
pembrolizumab arm.
V. To compare time to HRQOL deterioration in global HRQOL, as measured by the FBISI-18
disease-related physical symptom subscale (FBISI-18 disease-related symptoms (DRS) in the
physical emotional domains [DRS-P]), between patients on the sacituzumab govitecan arm
versus the sacituzumab govitecan + pembrolizumab arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive sacituzumab govitecan intravenously (IV) over 1-3 hours on days 1
and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or
unacceptable toxicity. Patients additionally undergo blood sample collection and computed
tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
ARM B: Patients receive pembrolizumab IV over 30 minutes on day 1 and sacituzumab
govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in
the absence of disease progression or unacceptable toxicity. Patients additional undergo
blood sample collection, and CT or MRI throughout the study.
After completion of study treatment, patients are followed up for 5 years from the date
of randomization.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient must be ≥ 18 years of age
- Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patient must have locally advanced or metastatic urothelial cancer
- Patient must have histologically proven conventional urothelial carcinoma (UC) of
any urinary tract origin [any histologic subtype except neuroendocrine (small or
large cell)] are permitted so long as tumors include ≥ 1% urothelial histology).
NOTE: Pure non-urothelial histology is excluded
- Patient must have measurable disease per Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria. Baseline imaging must be obtained ≤ 35 days prior to
randomization
- Patient must have the following prior treatment. Patient must have had progression
on or after the immediate prior therapy
- Patient must have had prior exposure to anti-PD(L)1 therapy [anti -PD(L)1
monotherapy or as a combination regimen in any disease/therapy setting for UC.
Patient must have received at least 1 dose of anti-PD(L)1 therapy
- NOTE: Anti-PD(L)1 therapy does not need to be the most recent therapy received
prior to enrollment on this protocol
- NOTE: Prior platinum-based chemotherapy and/or enfortumab vedotin is allowed in
any prior disease/therapy setting
- Patient must have had ≤ 2 lines of systemic therapy given in the advanced/metastatic
disease setting for tumors with no known FGFR2 or FGFR3 (-) susceptible alteration
(for erdafitinib) OR ≤ 3 lines of systemic therapy given in the advanced/metastatic
disease setting for tumors harboring susceptible FGFR2 or FGFR3 susceptible
alteration (for erdafitinib)
- Patient must have had no prior exposure to sacituzumab govitecan or other TROP-2
directed therapies or antibody-drug conjugate that contains topo-isomerase I
inhibitor
- Patient must not have any history of grade 3 or higher immune-related adverse events
on prior anti-PD1/L1, with the exception of endocrinopathies on adequate hormone
repletion and clinically insignificant laboratory abnormalities
- Patient must have recovered (i.e., ≤ grade 1) from clinically significant AEs due to
previously administered systemic therapy agent.
- NOTE: Patients with ≤ grade 2 neuropathy, any grade of alopecia, or any grade
of non-clinically significant laboratory abnormality are exceptions to this
criterion and are allowed in this trial.
- Examples of non-clinically significant laboratory abnormalities include, but
are not limited to:
- Grade 2-3 lymphopenia
- Monocytosis
- Increase in amylase or lipase with no clinical correlation
- Any other grade 2-3 abnormal laboratory findings that have no clinical
relevance per the treating investigators.
- NOTE: If patient has undergone major surgery, they must have recovered
adequately from the toxicity and/or complications from the intervention prior
to randomization
- Patient must not be pregnant or breast-feeding due to the potential harm to an
unborn fetus and possible risk for adverse events in nursing infants with the
treatment regimens being used. All patients of childbearing potential must have a
blood test or urine study within 14 days prior to randomization to rule out
pregnancy. A patient of childbearing potential is defined as anyone, regardless of
sexual orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not undergone a
hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal
(amenorrhea following cancer therapy does not rule out childbearing potential) for
at least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months). Patient must not nurse infants while on protocol treatment and
for 4 months after the last dose of protocol treatment
- Patient must not expect to conceive or father children by using an accepted and
effective method(s) of contraception or by abstaining from sexual intercourse for
the duration of their participation in the study. Patients of childbearing potential
must continue contraceptive method(s) or abstain for 6 months after the last dose of
protocol treatment. Patients with partners who could become pregnant should use
effective contraception during therapy and for 3 months after the last dose of
protocol treatment
- Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC)
who have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
- Absolute neutrophil count (ANC) ≥ 1,500/mcL (obtained ≤ 14 days prior to
randomization)
- Platelets ≥ 100,000/mcL (obtained ≤ 14 days prior to randomization)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 14
days prior to randomization)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤
3 × institutional ULN or ≤ 5.0 x institutional ULN if known liver metastases
(obtained ≤ 14 days prior to randomization)
- Creatinine clearance (CrCl) or estimated glomerular filtration rate (GFR) ≥ 30
ml/min (obtained ≤ 14 days prior to randomization) NOTE: CrCl is measured by 24-
hour urine collection or other validated instruments (e.g., Modification of Diet in
Renal Disease [MDRD] equation) and estimated (e)GFR estimated by the Cockcroft-Gault
formula
- Patient must not have a known genetic UGT1A1 deficiency (Gilbert's syndrome).
Patients with variant type UGT1A1*28 allele may have increased levels of SN-38
metabolite (due to reduced SN-38 metabolism and clearance) and are at higher risk
for severe adverse events when compared to wild-type.
- NOTE: If a patient's UGT1A1 status is unknown, they are eligible to enroll (the
study does not require this test as part of screening)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of randomization are eligible
for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression and
are not using steroids > 20 mg of prednisone (or equivalent) daily for brain
metastases for at least 7 days prior to randomization
- Patients with a prior or concurrent malignancy that is not considered clinically
significant and whose natural history or treatment does not have the potential to
interfere with the safety or efficacy assessment of the investigational regimen (at
the discretion of the treating physician) are eligible for this trial
- Patient must not be on immunosuppressive medication, including steroids (if doses
exceed the equivalent of prednisone 10 mg daily, except those with treated brain
metastases, where up to 20 mg/day is allowed). Short courses of steroids which are
discontinued prior to randomization are acceptable. Patients on inhaled, intranasal
and/or topical steroids are eligible
- Patient must be English or Spanish speaking to be eligible for the HRQOL component
of the study.
- NOTE: Sites cannot translate the associated HRQOL forms
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
February 6, 2025
Completion date:
December 31, 2028
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06524544
