A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)

• ClinicalTrials.gov Identifier: NCT03474107
• Recruitment Status: Active, not recruiting
• First Posted: March 22, 2018
• Results First Posted: August 24, 2021
• Last Update Posted: April 30, 2024
• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborator: Seagen Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ureteral Cancer; Urothelial Cancer; Bladder Cancer	Drug: Enfortumab Vedotin; Drug: Docetaxel; Drug: Vinflunine; Drug: Paclitaxel	Phase 3

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Detailed Description:

Japan PMDA has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.

Participants considered an adult according to local regulation at the time of obtaining informed consent participated in the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 608 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: June 27, 2018
• Actual Primary Completion Date: July 15, 2020
• Estimated Study Completion Date: August 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: Enfortumab Vedotin 1.25 mg/kg; Participants 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.	Drug: Enfortumab Vedotin; Intravenous infusion; Other Names: ASG-22ME; ASG-22CE
Active Comparator: Arm B: Chemotherapy; Participants 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.	Drug: Docetaxel; Intravenous infusion; Drug: Vinflunine; Intravenous infusion; Drug: Paclitaxel; Intravenous infusion
Experimental: Cross-over Extension (COE); Eligible 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.	Drug: Enfortumab Vedotin; Intravenous infusion; Other Names: ASG-22ME; ASG-22CE

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]
   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.

Secondary Outcome Measures :

1. Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]
   PFS: time from date of randomization until date of documented radiological disease progression (PD) per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last radiological assessment (RA)/ date of randomization if no post-baseline RA was available. Participants who received any further anticancer therapy (ACT) for disease before radiological progression was censored at date of last RA before ACT started and participants who had PD/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow-up for PFS was based on data cut-off & is same as median follow-up time for OS.
2. Overall Response Rate (ORR) as Per RECIST V1.1 [ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]
   ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. ORR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for ORR was based on data cut-off and is same as median follow-up time for OS.
3. Disease Control Rate (DCR) as Per RECIST V1.1 [ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]
   DCR was defined as the percentage of participants with a CR, PR or a stable disease (SD) based on RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. Progressive disease is defined in PFS1 endpoint. DCR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for DCR was based on data cut-off and is same as median follow-up time for OS.
4. Duration of Response (DOR) as Per RECIST V1.1 [ Time Frame: From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]
   DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by investigator to the date of documented PD or death due to any cause whichever occurred first. If a participant has neither progressed nor died, the participant was censored at the date of last RA or at the date of first CR/PR if no subsequent post-baseline RA was available. Participants who received any further ACT for the disease before radiological progression were censored at the date of the last RA before the ACT started. In addition, participants who had PD/death after >= 2 missed RAs were censored at the last RA prior to the 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow up for DOR was based on data cut-off and is same as median follow-up time for OS. CR/PR and PD were defined in ORR and PFS1 endpoints, respectively.
5. 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) [ Time Frame: Baseline and week 12 ]
   EORTC QLQ-C30 is a generic questionnaire consisting of 30 items. The instrument yields functional scales (physical, role, emotional, cognitive, social), symptom scales/items (fatigue, Nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), global health status, and financial impact score. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). The recall period for each question is "during the past week". All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Higher scores on the global health status and functioning scales indicate better health status/function.
6. Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS) [ Time Frame: Baseline and week 12 ]
   EQ-5D-5L is a health status instrument for self-reported assessment of 5 domains of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain is rated by selecting 1 of 5 standardized categorizations ranging from no problem to extreme problem. The final question is a visual analogue scale (VAS) to rank health status from 0 (best health imaginable) to 100 (worst health imaginable).
7. Number of Participants With Treatment Emergent Adverse Events [ Time Frame: From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group) ]
   An AE is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE is defined as an AE observed or worsened after starting administration of the study drug.
8. Number of Participants With ECOG Performance Status [ Time Frame: End of treatment (EOT) (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group) ]

   ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction.

   1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
   2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
   3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
   4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
   5. Dead. Number of participants with ECOG PS was reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

UCI Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

University of California

Sacramento, California, United States, 95817

Innovative Clinical Research

Whittier, California, United States, 90606

United States, Colorado

University of Colorado

Denver, Colorado, United States, 80045

United States, Connecticut

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States, 06510

United States, Florida

Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

Florida Hospital

Orlando, Florida, United States, 32804

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40207

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Nebraska

Nebraska Cancer Specialists

Omaha, Nebraska, United States, 68130

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Long Island Jewish Medical Center

Lake Success, New York, United States, 11042

Sidney Kimmel Center for Prostate and Urologic Cancers

New York, New York, United States, 10065

White Plains Hospital Center for Cancer Care - Oncology Site

White Plains, New York, United States, 10601

United States, Ohio

Toledo Clinic Cancer Center

Toledo, Ohio, United States, 43623

United States, Oregon

Providence Portland Med Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Rhode Island

Lifespan Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

Saint Francis Hospital

Greenville, South Carolina, United States, 29607

United States, Texas

HOPE Cancer Center of East Texas

Tyler, Texas, United States, 75701

United States, Washington

Benaroya Research Institute at Virginia Mason

Seattle, Washington, United States, 98101

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Argentina

Site AR54001

Buenos Aires, Argentina

Australia

Site AU61006

Adelaide, Australia

Site AU61001

Miranda, Australia

Site AU61004

St. Leonards, Australia

Site AU61002

Sydney, Australia

Austria

Site AT43005

Linz, Austria

Site AT43001

Salzburg, Austria

Site AT43004

Wien, Austria

Belgium

Site BE32011

Aalst, Belgium

Site BE32007

Brussels, Belgium

Site BE32013

Brussels, Belgium

Site BE32010

Charleroi, Belgium

Site BE32001

Gent, Belgium

Site BE32008

Gent, Belgium

Site BE32005

Hasselt, Belgium

Site BE32003

Leuven, Belgium

Site BE32009

Liège, Belgium

Canada

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

Quebec, Canada

Site CA15008

Saskatoon, Canada

Site CA15001

Sherbrooke, Canada

Site CA15005

Toronto, Canada

Site CA15013

Vancouver, Canada

Denmark

Site DK45003

Aalborg, Denmark

Site DK45004

Copenhagen, Denmark

Site DK45001

Herlev, Denmark

France

Site FR33021

Besancon, 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-Mande, France

Site FR33002

Strasbourg, France

Site FR33019

Toulouse, France

Site FR33006

Villejuif, France

Germany

Site DE49011

Essen, Germany

Site DE49008

Heidelberg, Germany

Site DE49010

Münster, Germany

Site DE49003

Tübingen, Germany

Site DE49009

Würzburg, Germany

Italy

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

Japan

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, Japan

Site JP81002

Yokohama, Kanagawa, Japan

Site JP81005

Sendai, Miyagi, Japan

Site JP81016

Osakasayama, 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

Korea, Republic of

Site KR82006

Daejeon, Korea, Republic of

Site KR82007

Goyang-Si, Korea, Republic of

Site KR82012

Hwasun-gun, Korea, Republic of

Site KR82002

Incheon, Korea, Republic of

Site KR82001

Seongnam-si, Korea, Republic of

Site KR82003

Seoul, Korea, Republic of

Site KR82004

Seoul, Korea, Republic of

Site KR82008

Seoul, Korea, Republic of

Site KR82009

Seoul, Korea, Republic of

Site KR82010

Seoul, Korea, Republic of

Site KR82005

Shin, Korea, Republic of

Netherlands

Site NL31002

Amsterdam, Netherlands

Site NL31003

Amsterdam, Netherlands

Site NL31009

Nijmegen, Netherlands

Site NL31001

Tilburg, Netherlands

Portugal

Site PT35105

Lisboa, Portugal

Site PT35102

Lisbon, Portugal

Site PT35106

Porto, Portugal

Russian Federation

Site RU70002

Ivanovo, Russian Federation

Site RU70009

Obninsk, Russian Federation

Site RU70005

Omsk, Russian Federation

Site RU70015

Vologda, Russian Federation

Spain

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

Switzerland

Site CH41002

Bern, Switzerland

Site CH41001

Chur, Switzerland

Taiwan

Site TW88602

Kaohsiung, Taiwan

Site TW88605

Kaohsiung, Taiwan

Site TW88606

Taichung, Taiwan

Site TW88601

Tainan, Taiwan

Site TW88604

Taipei, Taiwan

Site TW88607

Taoyuan, Taiwan

United Kingdom

Site GB44005

London, United Kingdom

Site GB44006

London, United Kingdom

Site GB44002

Sheffield, United Kingdom

Site GB44011

Southampton, United Kingdom

Site GB44013

Sutton, United Kingdom

Site GB44004

Wirral, United Kingdom

Sponsors and Collaborators

Astellas Pharma Global Development, Inc.

Seagen Inc.

Investigators

• Study Director: Medical Director; Astellas Pharma Global Development, Inc.

  Study Documents (Full-Text)

Documents provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

Study Protocol  [PDF] September 14, 2020

Statistical Analysis Plan  [PDF] August 10, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Powles 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.

• Responsible Party: Astellas Pharma Global Development, Inc.
• ClinicalTrials.gov Identifier: NCT03474107
• Other Study ID Numbers: 7465-CL-0301; 2017-003344-21 ( EudraCT Number )
• First Posted: March 22, 2018
• Results First Posted: August 24, 2021
• Last Update Posted: April 30, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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 compounds 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. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (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.
• URL: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

antibody drug conjugate; enfortumab vedotin (EV); ASG-22ME; ASG-22CE; urothelial cancer

Additional relevant MeSH terms:

Ureteral Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Paclitaxel; Docetaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action