A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
NCT ID: NCT06524544
Last Updated: 2026-02-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
320 participants
INTERVENTIONAL
2025-12-02
2028-12-31
Brief Summary
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Detailed Description
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I. To compare overall survival (OS) between the therapy of physician choice (TPC) arm and the sacituzumab govitecan + pembrolizumab arm.
SECONDARY OBJECTIVES:
I. To compare the progression free survival (PFS) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm.
II. To evaluate overall response rate (ORR) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm.
III. To evaluate clinical benefit rate (complete response \[CR\]/partial response \[PR\] /stable disease \[SD\]) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm.
IV. To evaluate duration of response (DoR) between the TPC 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).
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 TPC 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 TPC 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 TPC 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 TPC 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 TPC arm versus the sacituzumab govitecan + pembrolizumab arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive TPC with carboplatin or cisplatin intravenously (IV) on day 1 and gemcitabine IV on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may alternately receive TPC with docetaxel IV on day 1 of each cycle or paclitaxel IV 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 sacituzumab govitecan IV over 1-3 hours on days 1 and 8 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 35 cycles or for 2 years of pembrolizumab in the absence of disease progression or unacceptable toxicity. Cycles of sacituzumab govitecan repeats 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 at 30 days then once a year for 5 years from the date of randomization.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (TPC chemotherapy)
Patients receive TPC with carboplatin or cisplatin IV on day 1 and gemcitabine IV on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may alternately receive TPC with docetaxel IV on day 1 of each cycle or paclitaxel IV 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.
Biospecimen Collection
Undergo blood sample collection
Carboplatin
Given IV
Cisplatin
Given IV
Computed Tomography
Undergo CT
Docetaxel
Given IV
Gemcitabine
Given IV
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Questionnaire Administration
Ancillary studies
Arm II (pembrolizumab, sacituzumab govitecan)
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.
Biospecimen Collection
Undergo blood sample collection
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Pembrolizumab
Given IV
Questionnaire Administration
Ancillary studies
Sacituzumab Govitecan
Given IV
Interventions
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Biospecimen Collection
Undergo blood sample collection
Carboplatin
Given IV
Cisplatin
Given IV
Computed Tomography
Undergo CT
Docetaxel
Given IV
Gemcitabine
Given IV
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Pembrolizumab
Given IV
Questionnaire Administration
Ancillary studies
Sacituzumab Govitecan
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Patient must have locally advanced (unresectable or not amenable to curative intent therapy) 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. Patients 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
* Patient must not have had progression within 12 weeks of using anti-PD(l) 1 therapy
* Patient must have had ≥ 1 line of systemic therapy given in the advanced/metastatic disease setting. For tumors with FGFR3 + susceptible alteration (for FGFR inhibitor), patients must have received a prior FGFR inhibitor unless contraindicated per physician discretion
* Patient must have received prior enfortumab vedotin in any disease/therapy setting unless contraindicated per physician
* 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, e.g. trastuzumab deruxtecan
* Patient must have Bellmunt score of 0-2. The Bellmunt score assesses a patient's risk and is calculated based upon ECOG PS, the hemogloblin level and presence of liver metastases
* Patient must not have any history of grade 3 or higher immune-related adverse events on prior anti-PD1/L1, except for endocrinopathies on adequate hormone therapy 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, except for endocrinopathies on adequate hormone therapy repletion
* 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:
* Lymphopenia or monopenia
* Lymphocytosis or monocytosis
* Increase in amylase or lipase with no clinical correlation
* Any other 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 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/uL (obtained ≤ 14 days prior to randomization)
* Platelets ≥ 100,000/uL (obtained ≤ 14 days prior to randomization)
* Albumin ≥ 3 g/dL (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 \[SGOT\]) and 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) ≥ 30 mL/min (obtained ≤ 14 days prior to randomization) NOTE: CrCl is estimated using the Cockcroft-Gault formula (or can be measured by 24-hour urine collection if needed)
* 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 considered 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 \> 10 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 systemic immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids, e.g. "burst", which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal, intra-articular 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Monika Joshi
Role: PRINCIPAL_INVESTIGATOR
ECOG-ACRIN Cancer Research Group
Locations
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Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, United States
Carle at The Riverfront
Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Carle Physician Group-Effingham
Effingham, Illinois, United States
Crossroads Cancer Center
Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Carle BroMenn Medical Center
Normal, Illinois, United States
Carle Cancer Institute Normal
Normal, Illinois, United States
Memorial Hospital East
Shiloh, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Mary Greeley Medical Center
Ames, Iowa, United States
McFarland Clinic - Ames
Ames, Iowa, United States
McFarland Clinic - Boone
Boone, Iowa, United States
Mercy Hospital
Cedar Rapids, Iowa, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, United States
McFarland Clinic - Jefferson
Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, United States
UofL Health Medical Center Northeast
Louisville, Kentucky, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, United States
Essentia Health Cancer Center
Duluth, Minnesota, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, United States
Essentia Health Sandstone
Sandstone, Minnesota, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Parkland Health Center - Farmington
Farmington, Missouri, United States
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Missouri Baptist Medical Center
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, United States
Community Hospital of Anaconda
Anaconda, Montana, United States
Billings Clinic Cancer Center
Billings, Montana, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, United States
Community Medical Center
Missoula, Montana, United States
Saint Barnabas Medical Center
Livingston, New Jersey, United States
Monmouth Medical Center
Long Branch, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Rutgers New Jersey Medical School
Newark, New Jersey, United States
Robert Wood Johnson University Hospital Somerset
Somerville, New Jersey, United States
Community Medical Center
Toms River, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, United States
Reading Hospital
West Reading, Pennsylvania, United States
Hematology Oncology Associates of Fredericksburg Inc
Fredericksburg, Virginia, United States
Virginia Cancer Institute
Richmond, Virginia, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
FHCC at EvergreenHealth
Kirkland, Washington, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States
FHCC at Northwest Hospital
Seattle, Washington, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
West Virginia University Charleston Division
Charleston, West Virginia, United States
Duluth Clinic Ashland
Ashland, Wisconsin, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2024-06208
Identifier Type: REGISTRY
Identifier Source: secondary_id
EA8231
Identifier Type: OTHER
Identifier Source: secondary_id
EA8231
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2024-06208
Identifier Type: -
Identifier Source: org_study_id
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