A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
4 other identifiers
interventional
608
18 countries
155
Brief Summary
The purpose of this study was to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy. This study compared progression-free survival on study therapy (PFS1); the overall response rate (ORR) and the disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of participants treated with EV to participants treated with chemotherapy. In addition, this study evaluated the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy and assessed the safety and tolerability of EV, as well as, the quality of life (QOL) and Patient Reported Outcomes (PRO) parameters.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2018
Longer than P75 for phase_3
155 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 16, 2018
CompletedFirst Posted
Study publicly available on registry
March 22, 2018
CompletedStudy Start
First participant enrolled
June 27, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2020
CompletedResults Posted
Study results publicly available
August 24, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 27, 2025
CompletedJanuary 9, 2026
December 1, 2025
2.1 years
March 16, 2018
July 7, 2021
December 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
OS was defined as the time from the date of randomization until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier.
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Secondary Outcomes (8)
Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Overall Response Rate (ORR) as Per RECIST V1.1
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Disease Control Rate (DCR) as Per RECIST V1.1
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Duration of Response (DOR) as Per RECIST V1.1
From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Change From Baseline to Week 12 in European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Global Health Status (QL2 Score)
Baseline and week 12
- +3 more secondary outcomes
Study Arms (3)
Arm A: Enfortumab Vedotin 1.25 mg/kg
EXPERIMENTALParticipants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
Arm B: Chemotherapy
ACTIVE COMPARATORParticipants received either 75 milligrams per square meter (mg/m\^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m\^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m\^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
Cross-over Extension (COE)
EXPERIMENTALEligible participants from chemotherapy arm who met the criteria for COE will receive 1.25 mg/kg of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle until discontinuation criteria is met.
Interventions
Intravenous infusion
Eligibility Criteria
You may qualify if:
- Subject is legally an adult according to local regulation at the time of signing informed consent.
- Subject has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.
- Subject must have experienced radiographic progression or relapse during or after a checkpoint inhibitor (CPI) (anti-programmed cell death protein 1 (PD1) or anti-programmed death-ligand 1 (PD-L1)) for locally advanced or metastatic disease. Subjects who discontinued CPI treatment due to toxicity are eligible provided that the subjects have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Subjects for whom the most recent therapy has been a non-CPI based regimen are eligible if the subjects have progressed/relapsed during or after the subjects most recent therapy. Locally advanced disease must not be amenable to resection with curative intent per the treating physician.
- Subject must have received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting subject must have progressed within 12 months of completion.
- Subject has radiologically documented metastatic or locally advanced disease at baseline.
- An archival tumor tissue sample should be available for submission to central laboratory prior to study treatment. If an archival tumor tissue sample is not available, a fresh tissue sample should be provided. If a fresh tissue sample cannot be provided due to safety concerns, enrollment into the study must be discussed with the medical monitor.
- Subject has ECOG PS of 0 or 1
- The subject has the following baseline laboratory data:
- absolute neutrophil count (ANC) ≥ 1500/mm3
- platelet count ≥ 100 × 10\^9/L
- hemoglobin ≥ 9 g/dL
- serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
- creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24 hour urine collection (glomerular filtration rate \[GFR\] can also be used instead of CrCl)
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 3 x ULN for subjects with liver metastases
- Female subject must either:
- +10 more criteria
You may not qualify if:
- Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
- Subject has active central nervous system (CNS) metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
- CNS metastases have been clinically stable for at least 6 weeks prior to screening
- If requiring steroid treatment for CNS metastases, the subject is on a stable dose ≤ 20 mg/day of prednisone or equivalent for at least 2 weeks
- Baseline scans show no evidence of new or enlarged brain metastasis
- Subject does not have leptomeningeal disease
- Subject has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery). Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated). Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy related colitis, uveitis, or pneumonitis or subjects with other immunotherapy related AEs requiring high doses of steroids (\> 20 mg/day of prednisone or equivalent) are excluded.
- Subject has prior treatment with EV or other monomethyl auristatin E (MMAE)-based Antibody drug conjugates (ADCs).
- Subject has received prior chemotherapy for urothelial cancer with all available study therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions where vinflunine is an approved therapy).
- Subject has received more than 1 prior chemotherapy regimen for locally advanced or metastatic urothelial cancer, including chemotherapy for adjuvant or neo-adjuvant disease if recurrence occurred within 12 months of completing therapy. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen.
- Subject has history of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
- Subject is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of EV. Routine antimicrobial prophylaxis is permitted.
- Subject has known active Hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or active hepatitis C (e.g., hepatitis C virus (HCV) Ribonucleic Acid (RNA) \[qualitative\] is detected).
- Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
- Subject has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Astellas Pharma Global Development, Inc.lead
- Seagen Inc.collaborator
Study Sites (158)
UCI Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of California
Sacramento, California, 95817, United States
Innovative Clinical Research
Whittier, California, 90606, United States
University of Colorado
Denver, Colorado, 80045, United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, 06510, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Florida Hospital
Orlando, Florida, 32804, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Norton Cancer Institute
Louisville, Kentucky, 40207, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Long Island Jewish Medical Center
Lake Success, New York, 11042, United States
Sidney Kimmel Center for Prostate and Urologic Cancers
New York, New York, 10065, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
White Plains Hospital Center for Cancer Care - Oncology Site
White Plains, New York, 10601, United States
Toledo Clinic Cancer Center
Toledo, Ohio, 43623, United States
Providence Portland Med Center
Portland, Oregon, 97213, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Lifespan Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Saint Francis Hospital
Greenville, South Carolina, 29607, United States
HOPE Cancer Center of East Texas
Tyler, Texas, 75701, United States
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98101, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Site AR54001
Buenos Aires, Argentina
Site AU61006
Adelaide, Australia
Site AU61001
Miranda, Australia
Site AU61004
St Leonards, Australia
Site AU61002
Sydney, Australia
Site AT43005
Linz, Austria
Site AT43001
Salzburg, Austria
Site AT43004
Vienna, Austria
Site BE32011
Aalst, Belgium
Site BE32007
Brussels, Belgium
Site BE32013
Brussels, Belgium
Site BE32010
Charleroi, Belgium
Site BE32001
Ghent, Belgium
Site BE32008
Ghent, Belgium
Site BE32005
Hasselt, Belgium
Site BE32003
Leuven, Belgium
Site BE32009
Liège, Belgium
Site CA15015
Calgary, Canada
Site CA15012
Edmonton, Canada
Site CA15014
London, Canada
Site CA15002
Montreal, Canada
Site CA15007
Montreal, Canada
Site CA15011
Oshawa, Canada
Site CA15004
Québec, Canada
Site CA15008
Saskatoon, Canada
Site CA15001
Sherbrooke, Canada
Site CA15005
Toronto, Canada
Site CA15013
Vancouver, Canada
Site DK45003
Aalborg, Denmark
Site DK45004
Copenhagen, Denmark
Site DK45001
Herlev, Denmark
Site FR33021
Besançon, France
Site FR33009
Bordeaux, France
Site FR33018
Bordeaux, France
Site FR33001
Brest, France
Site FR33016
Caen, France
Site FR33015
Lyon, France
Site FR33014
Marseille, France
Site FR33003
Nice, France
Site FR33022
Paris, France
Site FR33005
Pierre-Bénite, France
Site FR33004
Saint-Mandé, France
Site FR33002
Strasbourg, France
Site FR33019
Toulouse, France
Site FR33006
Villejuif, France
Site DE49011
Essen, Germany
Site DE49008
Heidelberg, Germany
Site DE49010
Münster, Germany
Site DE49003
Tübingen, Germany
Site DE49009
Würzburg, Germany
Site IT39008
Arezzo, Italy
Site IT39019
Cremona, Italy
Site IT39010
Milan, Italy
Site IT39025
Modena, Italy
Site IT39013
Pisa, Italy
Site IT39014
Reggio Emilia, Italy
Site IT39004
Terni, Italy
Site JP81010
Hirosaki, Aomori, Japan
Site JP81014
Kashiwa, Chiba, Japan
Site JP81007
Sapporo, Hokkaido, Japan
Site JP81026
Sapporo, Hokkaido, Japan
Site JP81020
Tsukuba, Ibaraki, Japan
Site JP81018
Morioka, Iwate, Japan
Site JP81009
Kita-gun, Kagawa-ken, Japan
Site JP81002
Yokohama, Kanagawa, Japan
Site JP81005
Sendai, Miyagi, Japan
Site JP81016
Sayama, Osaka, Japan
Site JP81024
Takatsuki, Osaka, Japan
Site JP81008
Bunkyo-ku, Tokyo, Japan
Site JP81012
Koto-ku, Tokyo, Japan
Site JP81013
Shinjuku-ku, Tokyo, Japan
Site JP81011
Ube, Yamaguchi, Japan
Site JP81015
Chiba, Japan
Site JP81019
Fukuoka, Japan
Site JP81023
Fukuoka, Japan
Site JP81004
Hiroshima, Japan
Site JP81001
Kyoto, Japan
Site JP81017
Niigata, Japan
Site JP81003
Okayama, Japan
Site JP81022
Osaka, Japan
Site JP81021
Tokushima, Japan
Site JP81006
Toyama, Japan
Site NL31002
Amsterdam, Netherlands
Site NL31003
Amsterdam, Netherlands
Site NL31009
Nijmegen, Netherlands
Site NL31001
Tilburg, Netherlands
Site PT35102
Lisbon, Portugal
Site PT35105
Lisbon, Portugal
Site PT35106
Porto, Portugal
Site RU70002
Ivanovo, Russia
Site RU70009
Obninsk, Russia
Site RU70005
Omsk, Russia
Site RU70015
Vologda, Russia
Site KR82006
Daejeon, South Korea
Site KR82007
Goyang-si, South Korea
Site KR82012
Hwasun-gun, South Korea
Site KR82002
Incheon, South Korea
Site KR82001
Seongnam-si, South Korea
Site KR82003
Seoul, South Korea
Site KR82004
Seoul, South Korea
Site KR82008
Seoul, South Korea
Site KR82009
Seoul, South Korea
Site KR82010
Seoul, South Korea
Site KR82005
Shin, South Korea
Site ES34010
Badajoz, Spain
Site ES34002
Badalona, Spain
Site ES34001
Barcelona, Spain
Site ES34012
Barcelona, Spain
Site ES34023
Barcelona, Spain
Site ES34014
Córdoba, Spain
Site ES34003
Madrid, Spain
Site ES34013
Madrid, Spain
Site ES34015
Madrid, Spain
Site ES34017
Madrid, Spain
Site ES34011
Manresa, Spain
Site ES34019
Pamplona, Spain
Site ES34005
Seville, Spain
Site ES34007
Valencia, Spain
Site ES34008
Valencia, Spain
Site CH41002
Bern, Switzerland
Site CH41001
Chur, Switzerland
Site TW88602
Kaohsiung City, Taiwan
Site TW88605
Kaohsiung City, Taiwan
Site TW88606
Taichung, Taiwan
Site TW88601
Tainan, Taiwan
Site TW88604
Taipei, Taiwan
Site TW88607
Taoyuan District, Taiwan
Site GB44005
London, United Kingdom
Site GB44006
London, United Kingdom
Site GB44004
Metropolitan Borough of Wirral, United Kingdom
Site GB44002
Sheffield, United Kingdom
Site GB44011
Southampton, United Kingdom
Site GB44013
Sutton, United Kingdom
Related Publications (2)
Rosenberg JE, Mamtani R, Sonpavde GP, Loriot Y, Duran I, Lee JL, Matsubara N, Vulsteke C, Castellano D, Sridhar SS, Pappot H, Gurney H, Bedke J, van der Heijden MS, Galli L, Keam B, Masumori N, Meran J, O'Donnell PH, Park SH, Grande E, Sengelov L, Uemura H, Skaltsa K, Campbell M, Matsangou M, Wu C, Hepp Z, McKay C, Powles T, Petrylak DP. Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy. Eur Urol. 2024 Jun;85(6):574-585. doi: 10.1016/j.eururo.2024.01.007. Epub 2024 Feb 28.
PMID: 38418343DERIVEDPowles T, Rosenberg JE, Sonpavde GP, Loriot Y, Duran I, Lee JL, Matsubara N, Vulsteke C, Castellano D, Wu C, Campbell M, Matsangou M, Petrylak DP. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021 Mar 25;384(12):1125-1135. doi: 10.1056/NEJMoa2035807. Epub 2021 Feb 12.
PMID: 33577729DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Global Development, Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Global Development, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
March 16, 2018
First Posted
March 22, 2018
Study Start
June 27, 2018
Primary Completion
July 15, 2020
Study Completion
November 27, 2025
Last Updated
January 9, 2026
Results First Posted
August 24, 2021
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.