A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitean-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
A Phase III Randomized Trial of Pembrolizumab in Combination With Sacituzumab Govitean-hziy vs Standard of Care in Anti-PD(L)1-Resistant Advanced Urothelial Cancer
3 other identifiers
interventional
320
1 country
148
Brief Summary
This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitean-hziy to standard of care 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 govitean-hziy is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug called govitean-hziy. Sacituzumab attaches to TROP2 positive tumor cells in a targeted way and delivers govitean-hziy to kill them. The usual treatment approach is treatment with chemotherapy such as cisplatin, carboplatin, gemcitabine, docetaxel or paclitaxel. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Giving pembrolizumab and sacituzumab govitean-hziy may be more effective than usual care of carboplatin or cisplatin with gemcitabine, docetaxel or paclitaxel in treating patients with locally advanced or metastatic urothelial cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2025
Typical duration for phase_3
148 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 26, 2024
CompletedFirst Posted
Study publicly available on registry
July 29, 2024
CompletedStudy Start
First participant enrolled
December 2, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
June 11, 2026
May 1, 2026
3.1 years
July 26, 2024
June 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall survival (OS)
OS will be characterized with the method of Kaplan-Meier and will be compared between the two treatment arms using stratified log-rank test. The hazard ratio (HR) will be estimated, and a 95% confidence interval (CI) will be reported.
From randomization to death due to any cause, assessed up to 5 years
Secondary Outcomes (5)
Progression-free survival (PFS)
From randomization to the earlier progression or death due to any cause, assessed up to 5 years
Overall response rate (ORR)
Up to 5 years
Clinical benefit rate (CBR)
Up to 5 years
Duration of response (DOR)
From the first occurrence of a documented objective response to disease progression or death, whichever occurs first, assessed up to 5 years
Incidence of adverse events (AEs)
Up to 30 days after last dose of study drug
Other Outcomes (3)
Change in National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBISI-18) summary score
At baseline and at 3, 6 and 12 months
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) summary score
At baseline and at 3, 6 and 12 months
Change in quality-adjusted survival (assessed by the European Quality of Life Five Dimension Five Level scale [EQ-5D-5L]).
At baseline and at 3, 6 and 12 months
Study Arms (2)
Arm I (TPC chemotherapy)
ACTIVE COMPARATORPatients 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.
Arm II (pembrolizumab, sacituzumab govitean-hziy)
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1 and sacituzumab govitean-hziy 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.
Interventions
Given IV
Given IV
Given IV
Undergo CT
Undergo MRI
Given IV
Undergo blood sample collection
Given IV
Given IV
Ancillary studies
Eligibility Criteria
You may qualify if:
- Patient must be ≥ 18 years of age
- Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patient must have locally advanced (unresectable and/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% conventional 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(s). Patient must have had progression on or after the immediate prior anti-cancer 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
- NOTE: Patient must not have had progression within 12 weeks of starting their first anti-PD(L) 1 therapy, even if anti-PD-(L)1 treatment was given in more than one lines of therapy
- Patient must have had ≥ 1 line of systemic therapy given in the advanced/metastatic disease setting, except for patients who had received anti-PD(L)1 + enfortumab vedotin in the localized disease setting (e.g., neoadjuvant and/or adjuvant) and had cancer progression within 12 months from the last systemic therapy dose
- For tumors with known 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 vedotinor any other Nectin-4 directed therapy or other MMAE-containing therapy in any disease/therapy setting unless contraindicated per physician
- Patient must have had no prior exposure to Sacituzumab govitean-hziy 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 on ECOG PS, hemogloblin level and presence of liver metastases
- Patient must not have history of grade 3 or higher immune-related adverse events on prior anti-PD1/L1, except for endocrinopathies on adequate hormone therapy repletion and/or clinically insignificant laboratory abnormalities
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (148)
Cancer Center at Saint Joseph's
Phoenix, Arizona, 85004, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
University of Illinois
Chicago, Illinois, 60612, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle BroMenn Medical Center
Normal, Illinois, 61761, United States
Carle Cancer Institute Normal
Normal, Illinois, 61761, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Springfield Clinic
Springfield, Illinois, 62702, United States
Springfield Memorial Hospital
Springfield, Illinois, 62781, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Mary Greeley Medical Center
Ames, Iowa, 50010, United States
McFarland Clinic - Ames
Ames, Iowa, 50010, United States
McFarland Clinic - Boone
Boone, Iowa, 50036, United States
Mercy Hospital
Cedar Rapids, Iowa, 52403, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501, United States
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129, United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202, United States
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245, United States
Louisiana Hematology Oncology Associates LLC
Baton Rouge, Louisiana, 70809, United States
Mary Bird Perkins Cancer Center - Metairie
Metairie, Louisiana, 70002, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118, United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Avera Cancer Institute at Marshall
Marshall, Minnesota, 56258, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Parkland Health Center - Farmington
Farmington, Missouri, 63640, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080, United States
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, 63127, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Monmouth Medical Center
Long Branch, New Jersey, 07740, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07101, United States
Robert Wood Johnson University Hospital Somerset
Somerville, New Jersey, 08876, United States
Community Medical Center
Toms River, New Jersey, 08755, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, 28791, United States
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Geisinger Cancer Center Dickson City
Dickson City, Pennsylvania, 18519, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
Saint Vincent Hospital
Erie, Pennsylvania, 16544, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601, United States
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
IRMC Cancer Center
Indiana, Pennsylvania, 15701, United States
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837, United States
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Mechanicsburg, Pennsylvania, 17050, United States
Forbes Hospital
Monroeville, Pennsylvania, 15146, United States
UPMC Hillman Cancer Center - Monroeville
Monroeville, Pennsylvania, 15146, United States
Allegheny Valley Hospital
Natrona Heights, Pennsylvania, 15065, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
UPMC-Saint Margaret
Pittsburgh, Pennsylvania, 15215, United States
West Penn Hospital
Pittsburgh, Pennsylvania, 15224, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania, 15237, United States
UPMC Cancer Center-Washington
Washington, Pennsylvania, 15301, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Avera Cancer Institute-Aberdeen
Aberdeen, South Dakota, 57401, United States
Avera Cancer Institute - Mitchell
Mitchell, South Dakota, 57301, United States
Avera Cancer Institute at Pierre
Pierre, South Dakota, 57501, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Avera Cancer Institute at Yankton
Yankton, South Dakota, 57078, United States
Houston Methodist San Jacinto Hospital
Baytown, Texas, 77521, United States
Houston Methodist Cypress Hospital
Cypress, Texas, 77429, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
Methodist Willowbrook Hospital
Houston, Texas, 77070, United States
Houston Methodist West Hospital
Houston, Texas, 77094, United States
Houston Methodist Saint John Hospital
Nassau Bay, Texas, 77058, United States
Houston Methodist Sugar Land Hospital
Sugar Land, Texas, 77479, United States
Houston Methodist The Woodlands Hospital
The Woodlands, Texas, 77385, United States
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Hematology Oncology Associates of Fredericksburg Inc
Fredericksburg, Virginia, 22408, United States
Virginia Cancer Institute
Richmond, Virginia, 23229, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
FHCC Overlake
Bellevue, Washington, 98004, United States
FHCC at EvergreenHealth
Kirkland, Washington, 98034, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
FHCC at Northwest Hospital
Seattle, Washington, 98133, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
West Virginia University Charleston Division
Charleston, West Virginia, 25304, United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Monika Joshi
ECOG-ACRIN Cancer Research Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2024
First Posted
July 29, 2024
Study Start
December 2, 2025
Primary Completion (Estimated)
December 31, 2028
Study Completion (Estimated)
December 31, 2028
Last Updated
June 11, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
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