Trial Outcomes & Findings for A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301) (NCT NCT03474107)

Last Updated: 2026-01-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

608 participants

Primary outcome timeframe

From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Results posted on

2026-01-09

Participant Flow

Adult participants with locally advanced or metastatic urothelial cancer (mUC) who had received a platinum-containing chemotherapy and had experienced disease progression or relapse during or following treatment with programmed cell death protein-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors.

Participants were stratified by Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs 1), regions of the world Western EU vs US vs Rest of World) and liver metastasis (Yes vs No).

Participant milestones

Participant milestones
Measure	Enfortumab Vedotin 1.25mg/kg Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous (IV) 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.	Chemotherapy Participants received either 75 milligram 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 3 hours 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.
Overall Study STARTED	301	307
Overall Study Treated	296	291
Overall Study COMPLETED	56	22
Overall Study NOT COMPLETED	245	285

Reasons for withdrawal

Reasons for withdrawal
Measure	Enfortumab Vedotin 1.25mg/kg Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous (IV) 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.	Chemotherapy Participants received either 75 milligram 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 3 hours 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.
Overall Study Adverse Event	42	46
Overall Study Death	2	2
Overall Study Lost to Follow-up	0	1
Overall Study Progressive Disease	177	180
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	15	27
Overall Study Physician Decision	7	22
Overall Study Miscellaneous	1	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enfortumab Vedotin 1.25 mg/kg n=301 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28day 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.	Chemotherapy n=307 Participants Participants received either 75 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 3 hours 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.	Total n=608 Participants Total of all reporting groups
Age, Continuous	66.52 Years STANDARD_DEVIATION 9.11 • n=8 Participants	66.81 Years STANDARD_DEVIATION 9.93 • n=7 Participants	66.67 Years STANDARD_DEVIATION 9.53 • n=15 Participants
Sex: Female, Male Female	63 Participants n=8 Participants	75 Participants n=7 Participants	138 Participants n=15 Participants
Sex: Female, Male Male	238 Participants n=8 Participants	232 Participants n=7 Participants	470 Participants n=15 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=8 Participants	24 Participants n=7 Participants	53 Participants n=15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	230 Participants n=8 Participants	238 Participants n=7 Participants	468 Participants n=15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	42 Participants n=8 Participants	45 Participants n=7 Participants	87 Participants n=15 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Asian	97 Participants n=8 Participants	103 Participants n=7 Participants	200 Participants n=15 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=8 Participants	1 Participants n=7 Participants	1 Participants n=15 Participants
Race (NIH/OMB) Black or African American	2 Participants n=8 Participants	2 Participants n=7 Participants	4 Participants n=15 Participants
Race (NIH/OMB) White	159 Participants n=8 Participants	155 Participants n=7 Participants	314 Participants n=15 Participants
Race (NIH/OMB) More than one race	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Unknown or Not Reported	43 Participants n=8 Participants	46 Participants n=7 Participants	89 Participants n=15 Participants
ECOG PS ECOG PS=0	120 participants n=8 Participants	124 participants n=7 Participants	244 participants n=15 Participants
ECOG PS ECOG PS=1	181 participants n=8 Participants	183 participants n=7 Participants	364 participants n=15 Participants
Liver Metastasis Liver Metastasis=No	208 participants n=8 Participants	212 participants n=7 Participants	420 participants n=15 Participants
Liver Metastasis Liver Metastasis=Yes	93 participants n=8 Participants	95 participants n=7 Participants	188 participants n=15 Participants
Region Western Europe	126 participants n=8 Participants	129 participants n=7 Participants	255 participants n=15 Participants
Region United States	43 participants n=8 Participants	44 participants n=7 Participants	87 participants n=15 Participants
Region Rest of the World	132 participants n=8 Participants	134 participants n=7 Participants	266 participants n=15 Participants

PRIMARY outcome

Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Population: FAS Population

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=301 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=307 Participants Participants received either 75 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 3 hours 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.
Overall Survival (OS)	12.88 months Interval 10.58 to 15.21	8.97 months Interval 8.05 to 10.74

SECONDARY outcome

Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Population: FAS Population

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=301 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=307 Participants Participants received either 75 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 3 hours 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.
Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	5.55 months Interval 5.32 to 5.82	3.71 months Interval 3.52 to 3.94

SECONDARY outcome

Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Population: Response Evaluable Set (RES): The RES was defined as all participants in the FAS who had measurable disease (per RECIST v1.1) per investigator at baseline.

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=288 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=296 Participants Participants received either 75 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 3 hours 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.
Overall Response Rate (ORR) as Per RECIST V1.1	40.6 percentage of participants Interval 34.9 to 46.54	17.9 percentage of participants Interval 13.71 to 22.76

SECONDARY outcome

Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Population: RES Population

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=288 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=296 Participants Participants received either 75 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 3 hours 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.
Disease Control Rate (DCR) as Per RECIST V1.1	71.9 percentage of participants Interval 66.3 to 76.99	53.4 percentage of participants Interval 47.52 to 59.17

SECONDARY outcome

Timeframe: From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Population: RES population with available data.

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=117 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=53 Participants Participants received either 75 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 3 hours 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.
Duration of Response (DOR) as Per RECIST V1.1	7.39 months Interval 5.59 to 9.46	8.11 months Interval 5.65 to 9.56

SECONDARY outcome

Timeframe: Baseline and week 12

Population: FAS population with available data.

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=127 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=102 Participants Participants received either 75 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 3 hours 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.
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)	-2.30 score on a scale Standard Deviation 18.02	-5.72 score on a scale Standard Deviation 16.04

SECONDARY outcome

Timeframe: Baseline and week 12

Population: FAS population with available data.

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).

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=124 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=102 Participants Participants received either 75 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 3 hours 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.
Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)	-1.8 score on a scale Standard Deviation 16.6	-5.3 score on a scale Standard Deviation 14.5

SECONDARY outcome

Timeframe: 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)

Population: The safety analysis set (SAF) consisted of all participants who received any amount of study drug, and was used for safety analyses.

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=296 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=291 Participants Participants received either 75 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 3 hours 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.
Number of Participants With Treatment Emergent Adverse Events	290 participants	288 participants

SECONDARY outcome

Timeframe: 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)

Population: Safety population with available data.

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.

Outcome measures

Outcome measures
Measure	Enfortumab Vedotin 1.25 mg/kg n=184 Participants Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV 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.	Chemotherapy n=219 Participants Participants received either 75 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 3 hours 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.
Number of Participants With ECOG Performance Status ECOG PS = 0	34 participants	57 participants
Number of Participants With ECOG Performance Status ECOG PS = 1	110 participants	118 participants
Number of Participants With ECOG Performance Status ECOG PS >1	40 participants	44 participants

Adverse Events

Enfortumab Vedotin

Serious events: 138 serious events

Other events: 284 other events

Deaths: 130 deaths

Chemotherapy

Serious events: 128 serious events

Other events: 266 other events

Deaths: 161 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosure

Astellas Pharma Global Development, Inc.

Phone: 800-888-7704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Publication restrictions are in place

Restriction type: OTHER