New drug outshines chemo in advanced bladder cancer trial

NCT ID NCT03474107

Disease control Sponsor: Astellas Pharma Global Development, Inc. Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tested a new drug called enfortumab vedotin against standard chemotherapy in 608 adults with advanced bladder or urinary tract cancer that had spread or come back after prior treatment. The goal was to see if the new drug helped people live longer and slowed cancer growth. Results showed enfortumab vedotin improved survival and had a manageable safety profile, offering a new treatment option for this tough-to-treat cancer.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

608 people

The number who actually took part.

Started

Jun 2018

Finished

Nov 2025

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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: * Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). * Or, if of childbearing potential: Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration, and have a negative urine or serum pregnancy test within 7 days prior to Day 1 (Females with false positive results and documented verification of negative pregnancy status are eligible for participation), and if heterosexually active, agree to consistently use a condom plus 1 form of highly effective birth control per locally accepted standards starting at screening and throughout the study period and for at least 6 months after the final study drug administration. * Female subject must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 6 months after the final study drug administration. * A sexually active male subject with female partner(s) who is of childbearing potential is eligible if: * Agrees to use a male condom starting at screening and continue throughout the study treatment and for at least 6 months after final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below the subjects female partner(s) is utilizing 1 form of highly effective birth control per locally accepted standards starting at screening and continue throughout study treatment and for at least 6 months after the male subject receives final study drug administration. * Male subject must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final study drug administration. * Male subject with a pregnant or breastfeeding partner(s) must agree to abstinence or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for at least 6 months after the final study drug administration. * Subject agrees not to participate in another interventional study while on treatment in present study. Inclusion Criteria for COE: * Subject is eligible for the COE if they continue to meet all inclusion criteria from the main protocol in addition to the following when the patient is evaluated for eligibility to participate in the COE portion of the study: * Institutional review board (IRB)/ independent ethics committee (IEC) approved written COE informed consent and privacy language as per national regulations (e.g., health insurance portability and accountability act \[HIPAA\] Authorization for US sites) must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). * Subject was randomized to Arm B and is either currently on study treatment or has discontinued study treatment due to intolerance, AE or progression of disease and has not started a new systemic anticancer treatment. Exclusion Criteria: * 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. * Subject has radiotherapy or major surgery within 4 weeks prior to first dose of study drug. * Subject has had chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug. * Subject has known hypersensitivity to EV or to any excipient contained in the drug formulation of EV; OR subject has known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells. * Subject has known hypersensitivity to the following: docetaxel or to any of the other excipients listed in product label, including polysorbate 80, paclitaxel or to any of the other excipients listed in product label, such as macrogolglycerol ricinoleate 35 (Ph.Eur.); and vinflunine or to any of the other excipients listed in product label such as other vinca alkaloids (vinblastine,vincristine, vindesine, vinorelbine). * Subject has known active keratitis or corneal ulcerations. * Subject has other underlying medical condition that would impair the ability of the subject to receive or tolerate the planned treatment and follow-up. * History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c between 7 and \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. Exclusion Criteria for COE * Subject will be excluded from participation in the COE if they meet any of the exclusion criteria listed in the main protocol or if any of the following apply when the patient is evaluated for eligibility to participate in the COE portion of the study: * Subject has been diagnosed with a new malignancy while on Arm B in the EV-301 study. 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 has already started commercial EV or arrangements have been made for subject to start commercial EV which is reimbursed in their country. Additionally, if EV is commercially available with reimbursement in the potential subject's country, the subject can consider transitioning to the commercial product unless otherwise discussed with sponsor.

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Conditions

The condition(s) this trial relates to.

ureter cancer urinary bladder carcinoma Urinary Bladder Neoplasms urothelial carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Bladder cancer Ureteral cancer Urothelial cancer

Contacts and locations

Locations

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Florida Hospital

Orlando, Florida, 32804, United States
Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States
HOPE Cancer Center of East Texas

Tyler, Texas, 75701, United States
Innovative Clinical Research

Whittier, California, 90606, United States
Lifespan Rhode Island Hospital

Providence, Rhode Island, 02903, United States
Long Island Jewish Medical Center

Lake Success, New York, 11042, United States
Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Montefiore Medical Center

The Bronx, New York, 10467, United States
Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States
Norton Cancer Institute

Louisville, Kentucky, 40207, United States
Providence Portland Med Center

Portland, Oregon, 97213, United States
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Rush University Medical Center

Chicago, Illinois, 60612, United States
Saint Francis Hospital

Greenville, South Carolina, 29607, United States
Sidney Kimmel Center for Prostate and Urologic Cancers

New York, New York, 10065, United States
Site AR54001

Buenos Aires, Argentina
Site AT43001

Salzburg, Austria
Site AT43004

Vienna, Austria
Site AT43005

Linz, Austria
Site AU61001

Miranda, Australia
Site AU61002

Sydney, Australia
Site AU61004

St Leonards, Australia
Site AU61006

Adelaide, Australia
Site BE32001

Ghent, Belgium
Site BE32003

Leuven, Belgium
Site BE32005

Hasselt, Belgium
Site BE32007

Brussels, Belgium
Site BE32008

Ghent, Belgium
Site BE32009

Liège, Belgium
Site BE32010

Charleroi, Belgium
Site BE32011

Aalst, Belgium
Site BE32013

Brussels, Belgium
Site CA15001

Sherbrooke, Canada
Site CA15002

Montreal, Canada
Site CA15004

Québec, Canada
Site CA15005

Toronto, Canada
Site CA15007

Montreal, Canada
Site CA15008

Saskatoon, Canada
Site CA15011

Oshawa, Canada
Site CA15012

Edmonton, Canada
Site CA15013

Vancouver, Canada
Site CA15014

London, Canada
Site CA15015

Calgary, Canada
Site CH41001

Chur, Switzerland
Site CH41002

Bern, Switzerland
Site DE49003

Tübingen, Germany
Site DE49008

Heidelberg, Germany
Site DE49009

Würzburg, Germany
Site DE49010

Münster, Germany
Site DE49011

Essen, Germany
Site DK45001

Herlev, Denmark
Site DK45003

Aalborg, Denmark
Site DK45004

Copenhagen, Denmark
Site ES34001

Barcelona, Spain
Site ES34002

Badalona, Spain
Site ES34003

Madrid, Spain
Site ES34005

Seville, Spain
Site ES34007

Valencia, Spain
Site ES34008

Valencia, Spain
Site ES34010

Badajoz, Spain
Site ES34011

Manresa, Spain
Site ES34012

Barcelona, Spain
Site ES34013

Madrid, Spain
Site ES34014

Córdoba, Spain
Site ES34015

Madrid, Spain
Site ES34017

Madrid, Spain
Site ES34019

Pamplona, Spain
Site ES34023

Barcelona, Spain
Site FR33001

Brest, France
Site FR33002

Strasbourg, France
Site FR33003

Nice, France
Site FR33004

Saint-Mandé, France
Site FR33005

Pierre-Bénite, France
Site FR33006

Villejuif, France
Site FR33009

Bordeaux, France
Site FR33014

Marseille, France
Site FR33015

Lyon, France
Site FR33016

Caen, France
Site FR33018

Bordeaux, France
Site FR33019

Toulouse, France
Site FR33021

Besançon, France
Site FR33022

Paris, France
Site GB44002

Sheffield, United Kingdom
Site GB44004

Metropolitan Borough of Wirral, United Kingdom
Site GB44005

London, United Kingdom
Site GB44006

London, United Kingdom
Site GB44011

Southampton, United Kingdom
Site GB44013

Sutton, United Kingdom
Site IT39004

Terni, Italy
Site IT39008

Arezzo, Italy
Site IT39010

Milan, Italy
Site IT39013

Pisa, Italy
Site IT39014

Reggio Emilia, Italy
Site IT39019

Cremona, Italy
Site IT39025

Modena, Italy
Site JP81001

Kyoto, Japan
Site JP81002

Yokohama, Kanagawa, Japan
Site JP81003

Okayama, Japan
Site JP81004

Hiroshima, Japan
Site JP81005

Sendai, Miyagi, Japan
Site JP81006

Toyama, Japan
Site JP81007

Sapporo, Hokkaido, Japan
Site JP81008

Bunkyo-ku, Tokyo, Japan
Site JP81009

Kita-gun, Kagawa-ken, Japan
Site JP81010

Hirosaki, Aomori, Japan
Site JP81011

Ube, Yamaguchi, Japan
Site JP81012

Koto-ku, Tokyo, Japan
Site JP81013

Shinjuku-ku, Tokyo, Japan
Site JP81014

Kashiwa, Chiba, Japan
Site JP81015

Chiba, Japan
Site JP81016

Sayama, Osaka, Japan
Site JP81017

Niigata, Japan
Site JP81018

Morioka, Iwate, Japan
Site JP81019

Fukuoka, Japan
Site JP81020

Tsukuba, Ibaraki, Japan
Site JP81021

Tokushima, Japan
Site JP81022

Osaka, Japan
Site JP81023

Fukuoka, Japan
Site JP81024

Takatsuki, Osaka, Japan
Site JP81026

Sapporo, Hokkaido, Japan
Site KR82001

Seongnam-si, South Korea
Site KR82002

Incheon, South Korea
Site KR82003

Seoul, South Korea
Site KR82004

Seoul, South Korea
Site KR82005

Shin, South Korea
Site KR82006

Daejeon, South Korea
Site KR82007

Goyang-si, South Korea
Site KR82008

Seoul, South Korea
Site KR82009

Seoul, South Korea
Site KR82010

Seoul, South Korea
Site KR82012

Hwasun-gun, South Korea
Site NL31001

Tilburg, Netherlands
Site NL31002

Amsterdam, Netherlands
Site NL31003

Amsterdam, Netherlands
Site NL31009

Nijmegen, Netherlands
Site PT35102

Lisbon, Portugal
Site PT35105

Lisbon, Portugal
Site PT35106

Porto, Portugal
Site RU70002

Ivanovo, Russia
Site RU70005

Omsk, Russia
Site RU70009

Obninsk, Russia
Site RU70015

Vologda, Russia
Site TW88601

Tainan, Taiwan
Site TW88602

Kaohsiung City, Taiwan
Site TW88604

Taipei, Taiwan
Site TW88605

Kaohsiung City, Taiwan
Site TW88606

Taichung, Taiwan
Site TW88607

Taoyuan, Taiwan
Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States
Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States
Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States
UCI Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States
University of California

Sacramento, California, 95817, United States
University of Colorado

Denver, Colorado, 80045, United States
University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States
White Plains Hospital Center for Cancer Care - Oncology Site

White Plains, New York, 10601, United States

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