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

Bladder Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03474107
• Other study ID #: 7465-CL-0301
• Secondary ID: 2017-003344-21
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 27, 2018
• Est. completion date: August 31, 2024

Study information

• Verified date: May 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 608
• Est. completion date: August 31, 2024
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Cancer
• Ureteral Cancer
• Ureteral Neoplasms
• Urothelial Cancer

Intervention

Drug:
• Enfortumab Vedotin
Intravenous infusion
• Docetaxel
Intravenous infusion
• Vinflunine
Intravenous infusion
• Paclitaxel
Intravenous infusion

Locations

Country	Name	City	State
Argentina	Site AR54001	Buenos Aires
Australia	Site AU61006	Adelaide
Australia	Site AU61001	Miranda
Australia	Site AU61004	St. Leonards
Australia	Site AU61002	Sydney
Austria	Site AT43005	Linz
Austria	Site AT43001	Salzburg
Austria	Site AT43004	Wien
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
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
Denmark	Site DK45003	Aalborg
Denmark	Site DK45004	Copenhagen
Denmark	Site DK45001	Herlev
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
Germany	Site DE49011	Essen
Germany	Site DE49008	Heidelberg
Germany	Site DE49010	Münster
Germany	Site DE49003	Tübingen
Germany	Site DE49009	Würzburg
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
Japan	Site JP81008	Bunkyo-ku	Tokyo
Japan	Site JP81015	Chiba
Japan	Site JP81019	Fukuoka
Japan	Site JP81023	Fukuoka
Japan	Site JP81010	Hirosaki	Aomori
Japan	Site JP81004	Hiroshima
Japan	Site JP81014	Kashiwa	Chiba
Japan	Site JP81009	Kita-gun	Kagawa
Japan	Site JP81012	Koto-ku	Tokyo
Japan	Site JP81001	Kyoto
Japan	Site JP81018	Morioka	Iwate
Japan	Site JP81017	Niigata
Japan	Site JP81003	Okayama
Japan	Site JP81022	Osaka
Japan	Site JP81016	Osakasayama	Osaka
Japan	Site JP81007	Sapporo	Hokkaido
Japan	Site JP81026	Sapporo	Hokkaido
Japan	Site JP81005	Sendai	Miyagi
Japan	Site JP81013	Shinjuku-ku	Tokyo
Japan	Site JP81024	Takatsuki	Osaka
Japan	Site JP81021	Tokushima
Japan	Site JP81006	Toyama
Japan	Site JP81020	Tsukuba	Ibaraki
Japan	Site JP81011	Ube	Yamaguchi
Japan	Site JP81002	Yokohama	Kanagawa
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
Netherlands	Site NL31002	Amsterdam
Netherlands	Site NL31003	Amsterdam
Netherlands	Site NL31009	Nijmegen
Netherlands	Site NL31001	Tilburg
Portugal	Site PT35105	Lisboa
Portugal	Site PT35102	Lisbon
Portugal	Site PT35106	Porto
Russian Federation	Site RU70002	Ivanovo
Russian Federation	Site RU70009	Obninsk
Russian Federation	Site RU70005	Omsk
Russian Federation	Site RU70015	Vologda
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
Switzerland	Site CH41002	Bern
Switzerland	Site CH41001	Chur
Taiwan	Site TW88602	Kaohsiung
Taiwan	Site TW88605	Kaohsiung
Taiwan	Site TW88606	Taichung
Taiwan	Site TW88601	Tainan
Taiwan	Site TW88604	Taipei
Taiwan	Site TW88607	Taoyuan
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 States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Colorado	Denver	Colorado
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Long Island Jewish Medical Center	Lake Success	New York
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut
United States	Sidney Kimmel Center for Prostate and Urologic Cancers	New York	New York
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	UCI Chao Family Comprehensive Cancer Center	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Providence Portland Med Center	Portland	Oregon
United States	Lifespan Rhode Island Hospital	Providence	Rhode Island
United States	University of California	Sacramento	California
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	HOPE Cancer Center of East Texas	Tyler	Texas
United States	White Plains Hospital Center for Cancer Care - Oncology Site	White Plains	New York
United States	Innovative Clinical Research	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Seagen Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Russian Federation,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	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.	From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Secondary	Overall Response Rate (ORR) as Per RECIST V1.1	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.	From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Secondary	Disease Control Rate (DCR) as Per RECIST V1.1	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.	From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Secondary	Duration of Response (DOR) as Per RECIST V1.1	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.	From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Secondary	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)	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.	Baseline and week 12
Secondary	Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)	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).	Baseline and week 12
Secondary	Number of Participants With Treatment Emergent Adverse Events	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.	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)
Secondary	Number of Participants With ECOG Performance Status	ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction.; 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.; Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.; Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.; Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.; Dead. Number of participants with ECOG PS was reported.	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)