A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer
NCT ID: NCT03288545
Last Updated: 2025-11-10
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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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
348 participants
INTERVENTIONAL
2017-10-11
2026-09-11
Brief Summary
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Detailed Description
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Locally advanced or metastatic urothelial cancer:
* Dose escalation
* Expansion
* Part 1: Cohorts A and Optional B
* Part 2: Cohorts D, E, and Optional F
* Part 3: Cohort G.
* Randomized Cohort K
* EV Monotherapy Arm
* EV Combination Arm
Muscle invasive bladder cancer:
* Cohort H
* Optional Cohort J
* Cohort L
Conditions
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Keywords
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L
Dose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
Cohort D: Enfortumab Vedotin + Cisplatin in 1L
Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
cisplatin
IV infusion on day 1 every 21 days
Cohort E: Enfortumab Vedotin + Carboplatin in 1L
Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
carboplatin
IV infusion on day 1 every 21 days
Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L
Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
gemcitabine
IV infusion on days 1 and 8 every 21 days
Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
cisplatin
IV infusion on day 1 every 21 days
carboplatin
IV infusion on day 1 every 21 days
Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting
Enfortumab vedotin on days 1 and 8 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
Randomized Cohort K: Enfortumab Vedotin Monotherapy
Enfortumab vedotin on days 1 and 8 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
Cohort L: Enfortumab vedotin in MIBC in perioperative setting
Enfortumab vedotin on days 1 and 8 and every 21 days
enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
Interventions
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enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
pembrolizumab
IV infusion on day 1 every 21 days
cisplatin
IV infusion on day 1 every 21 days
carboplatin
IV infusion on day 1 every 21 days
gemcitabine
IV infusion on days 1 and 8 every 21 days
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Histologically documented la/mUC, including squamous differentiation or mixed cell types.
* An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
* Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
* Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
* Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
* Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
* Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
* Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
* Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
* Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
* Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) \<60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
* Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.
* Histologically confirmed MIBC with predominant \>50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (\>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.
* Must be cisplatin-ineligible.
* Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
* ECOG performance status of 0, 1, or 2.
* Anticipated life expectancy of ≥3 months.
* Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
* Participants must be deemed eligible for RC+PLND.
Exclusion Criteria
* Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
* Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
* Ongoing sensory or motor neuropathy Grade 2 or higher.
* Active central nervous system (CNS) metastases.
* Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
* Conditions requiring high doses of steroids or other immunosuppressive medications.
* Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
* Uncontrolled diabetes mellitus.
* MIBC - Cohorts H, J, and L
* Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
* Received any prior treatment with a CPI.
* Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
* For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
* Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
* Ongoing sensory or motor neuropathy Grade 2 or higher.
* Conditions requiring high doses of steroids or other immunosuppressive medications.
* Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
* Participants with a history of another invasive malignancy within 3 years before first dose of study drug.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Seagen Inc.
INDUSTRY
Astellas Pharma Global Development, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Changting Meng, MD
Role: STUDY_DIRECTOR
Seagen Inc.
Jason Lukas, MD, PhD
Role: STUDY_DIRECTOR
Seagen Inc.
Locations
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Alaska Urological Institute
Anchorage, Alaska, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Mayo Clinic Arizona
Phoenix, Arizona, United States
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, United States
Highlands Oncology Group
Fayetteville, Arkansas, United States
Tower Hematology Oncology Medical Group
Beverly Hills, California, United States
UC San Diego / Moores Cancer Center
La Jolla, California, United States
University of California Irvine - Newport
Orange, California, United States
University of California, Davis Comprehensive Cancer Center
Sacramento, California, United States
University of California at San Francisco
San Francisco, California, United States
Saint Joseph Heritage Medical Group
Santa Rosa, California, United States
Stanford Cancer Center / Blood & Marrow Transplant Program
Stanford, California, United States
Kaiser Permanente Southern California
Woodland Hills, California, United States
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado, United States
University of Colorado Hospital / University of Colorado
Aurora, Colorado, United States
Yale Cancer Center
New Haven, Connecticut, United States
Eastern CT Hematology and Oncology Associates
Norwich, Connecticut, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Boca Raton Regional Hospital / Lynn Cancer Institute
Boca Raton, Florida, United States
Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale, Florida, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
Piedmont Cancer Institute
Atlanta, Georgia, United States
Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Decatur Memorial Hospital - Illinois
Decatur, Illinois, United States
Northwestern Medicine Cancer Center - Kishwaukee / Kishwaukee Cancer Center
DeKalb, Illinois, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
Cardinal Bernardin Cancer Center / Loyola University Medical Center
Maywood, Illinois, United States
Northwestern Medicine Cancer Center - Warrenville / Central DuPage Hospital - Cancer Care
Warrenville, Illinois, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
Tulane University Hospital and Clinic
New Orleans, Louisiana, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Maryland Oncology Hematology, P.A.
Silver Spring, Maryland, United States
Southcoast Centers for Cancer Care - Fairhaven Site
Fairhaven, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
McLaren Greater Lansing Hospital
Lansing, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, United States
Nebraska Hematology Oncology P.C.
Lincoln, Nebraska, United States
OptumCare Cancer Center
Las Vegas, Nevada, United States
Memorial Sloan Kettering Cancer Center - Basking Ridge
Basking Ridge, New Jersey, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center - Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center - Bergen
Montvale, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
New York Oncology Hematology, P.C.
Albany, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center - Commack
Commack, New York, United States
Memorial Sloan Kettering Cancer Center - Westchester
Harrison, New York, United States
Northwell Cancer Center / Monter Cancer Center
Lake Success, New York, United States
NYU Winthrop Hospital
Mineola, New York, United States
New York University (NYU) Cancer Institute
New York, New York, United States
Weill Cornell Medical College
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Memorial Sloan Kettering Cancer Center - Nassau
Uniondale, New York, United States
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
Chapel Hill, North Carolina, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Vidant Medical Center
Greenville, North Carolina, United States
Gabrail Cancer Center Research, LLC
Canton, Ohio, United States
Case Western Reserve University / University Hospitals Case Medical Center
Cleveland, Ohio, United States
Toledo Clinic Cancer Center
Toledo, Ohio, United States
CMOH Broomall
Broomall, Pennsylvania, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina/Hollings Cancer Center
Charleston, South Carolina, United States
Saint Francis Hospital Cancer Center
Greenville, South Carolina, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States
Sarah Cannon Research Institute
Chattanooga, Tennessee, United States
Tennessee Oncology / Sarah Cannon Research Institute
Nashville, Tennessee, United States
Texas Oncology - Fort Worth Cancer Center
Fort Worth, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Texas Oncology - Tyler
Tyler, Texas, United States
Utah Cancer Specialists
Salt Lake City, Utah, United States
University of Virginia
Charlottesville, Virginia, United States
Virginia Oncology Associates - Norfolk
Norfolk, Virginia, United States
Medical Oncology Associates
Spokane, Washington, United States
Medical College of Wisconsin (Milwaukee)
Milwaukee, Wisconsin, United States
Site CA11008
East Brampton, Ontario, Canada
Site CA11011
Kingston, Ontario, Canada
Site CA11001
Toronto, Ontario, Canada
Site CA11005
Montreal, Quebec, Canada
Site CA11013
Montreal, Quebec, Canada
Site CA11002
Sherbrooke, Quebec, Canada
Site FR33008
Bordeaux, , France
Site FR33005
Dijon, , France
Site FR33003
Lyon, , France
Site FR33004
Marseille, , France
Site FR33010
Moselle, , France
Site FR33002
Nice, , France
Site FR33006
Pierre-BĂ©nite, , France
Site FR33001
Strasbourg, , France
Site IT39002
Terni, , Italy
Site PR78701
Rio Piedras, , Puerto Rico
Site ES34006
Barcelona, , Spain
Site ES34008
Madrid, , Spain
Site ES34001
Madrid, , Spain
Site ES34012
Madrid, , Spain
Site ES34007
Pamplona, , Spain
Site ES34005
Sabadell, , Spain
Site ES34004
Santander, , Spain
Countries
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References
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Milowsky MI, O'Donnell PH, Hoimes CJ, Petrylak DP, Flaig TW, Moon HH, Friedlander TW, Mar N, McKay RR, Srinivas S, Gravis G, Ramamurthy C, Bupathi M, Bracarda S, Wright P, Hepp Z, Carret AS, Yu Y, Dillon R, Kataria R, Beaumont JL, Purnajo I, Rosenberg JE. Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab. J Clin Oncol. 2024 Apr 20;42(12):1403-1414. doi: 10.1200/JCO.23.01547. Epub 2024 Jan 12.
O'Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N, Moon HH, Friedlander TW, McKay RR, Bilen MA, Srinivas S, Burgess EF, Ramamurthy C, George S, Geynisman DM, Bracarda S, Borchiellini D, Geoffrois L, Maroto Rey JP, Ferrario C, Carret AS, Yu Y, Guseva M, Homet Moreno B, Rosenberg JE. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023 Sep 1;41(25):4107-4117. doi: 10.1200/JCO.22.02887. Epub 2023 Jun 27.
Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, Bilen MA, Gupta S, Srinivas S, Merchan JR, McKay RR, Petrylak DP, Sasse C, Moreno BH, Yu Y, Carret AS, Rosenberg JE. Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. J Clin Oncol. 2023 Jan 1;41(1):22-31. doi: 10.1200/JCO.22.01643. Epub 2022 Aug 30.
Other Identifiers
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MK-3475-869
Identifier Type: OTHER
Identifier Source: secondary_id
KEYNOTE KN-869
Identifier Type: OTHER
Identifier Source: secondary_id
SGN22E-002
Identifier Type: -
Identifier Source: org_study_id