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CompletedNCT03474107Updated Jan 9, 2026Results posted

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

A Phase 3 interventional study of Enfortumab Vedotin and Docetaxel in Ureteral Cancer, Urothelial Cancer and Bladder Cancer, sponsored by Astellas Pharma Global Development, Inc.. Completed at 158 sites in 19 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-09.

Sponsored by Astellas Pharma Global Development, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
608
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Ureteral Cancer
  • Urothelial Cancer
  • Bladder Cancer

Keywords

  • antibody drug conjugate
  • enfortumab vedotin (EV)
  • ASG-22ME
  • ASG-22CE
  • urothelial cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
608 participants (actual)

Study arms

  • 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

  • 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 · Drug: Vinflunine · Drug: Paclitaxel

  • 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

Interventions

  • DrugEnfortumab Vedotin

    Intravenous infusion

    Also known as: ASG-22ME, ASG-22CE

  • DrugDocetaxel

    Intravenous infusion

  • DrugVinflunine

    Intravenous infusion

  • DrugPaclitaxel

    Intravenous infusion

05

What researchers measure

Primary outcomes

  1. Overall Survival (OS)

    OS was defined as the time from the date of randomization until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier.

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

Secondary outcomes

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

    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)

  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)

    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.

    Time frame: Baseline and week 12

  6. 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).

    Time frame: Baseline and week 12

  7. 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.

    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)

  8. 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. 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.

    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)

06

Results

Posted Aug 24, 2021

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.

Participant flow — Overall Study
MilestoneEnfortumab Vedotin 1.25mg/kgChemotherapy
Started301307
Treated296291
Completed5622
Not completed245285
Withdrew: Adverse event4246
Withdrew: Death22
Withdrew: Lost to follow-up01
Withdrew: Progressive disease177180
Withdrew: Protocol violation11
Withdrew: Withdrawal by subject1527
Withdrew: Physician decision722
Withdrew: Miscellaneous16

Outcome measures

PrimaryOverall 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.

Time frame:
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Reported as:
Median · months
Overall Survival (OS)
monthsEnfortumab Vedotin 1.25 mg/kgChemotherapy
Overall Survival (OS)12.88 (10.58 to 15.21)8.97 (8.05 to 10.74)
Statistical analysis
  • Enfortumab Vedotin 1.25 mg/kg vs Chemotherapy · Stratified Log rank · p = 0.00142 (Stratification factors were ECOG PS, geographic region and liver metastasis. P-value was based on log-rank test. P-value of overall survival is ≤ the predetermined 1-sided significance level of 0.00679 based on the number of observed deaths.) · Stratified hazard ratio: 0.702 · 95% CI 0.556 to 0.886Cox proportional hazards model with treatment, ECOG PS, geographic region and liver metastasis as the explanatory variables.
SecondaryProgression 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.

Time frame:
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Reported as:
Median · months
Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
monthsEnfortumab Vedotin 1.25 mg/kgChemotherapy
Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)5.55 (5.32 to 5.82)3.71 (3.52 to 3.94)
Statistical analysis
  • Enfortumab Vedotin 1.25 mg/kg vs Chemotherapy · Stratified Log Rank · p = <0.00001 (Stratification factors were ECOG PS, geographic region and liver metastasis. P-value was based on log-rank test. P value of PFS is ≤ the predetermined 1-sided significance level of 0.02189 based on the number of observed PFS events.) · Stratified hazard ratio: 0.615 · 95% CI 0.505 to 0.748Cox proportional hazards model with treatment, ECOG PS, geographic region and liver metastasis as the explanatory variables.
SecondaryOverall 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.

Time frame:
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Reported as:
Number · percentage of participants
Overall Response Rate (ORR) as Per RECIST V1.1
percentage of participantsEnfortumab Vedotin 1.25 mg/kgChemotherapy
Overall Response Rate (ORR) as Per RECIST V1.140.6 (34.90 to 46.54)17.9 (13.71 to 22.76)
Statistical analysis
  • Enfortumab Vedotin 1.25 mg/kg vs Chemotherapy · Stratified Cochran-Mantel-Haenszel · p = <0.001 ("Stratification factors were ECOG PS, Region and Liver Metastasis.)
SecondaryDisease 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.

Time frame:
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
Reported as:
Number · percentage of participants
Disease Control Rate (DCR) as Per RECIST V1.1
percentage of participantsEnfortumab Vedotin 1.25 mg/kgChemotherapy
Disease Control Rate (DCR) as Per RECIST V1.171.9 (66.30 to 76.99)53.4 (47.52 to 59.17)
Statistical analysis
  • Enfortumab Vedotin 1.25 mg/kg vs Chemotherapy · Stratified Cochran-Mantel-Haenszel · p = <0.001 (Stratification factors were ECOG PS, Region and Liver Metastasis.)
SecondaryDuration 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.

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)
Reported as:
Median · months
Duration of Response (DOR) as Per RECIST V1.1
monthsEnfortumab Vedotin 1.25 mg/kgChemotherapy
Duration of Response (DOR) as Per RECIST V1.17.39 (5.59 to 9.46)8.11 (5.65 to 9.56)
SecondaryChange 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.

Time frame:
Baseline and week 12
Reported as:
Mean · score on a scale
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)
score on a scaleEnfortumab Vedotin 1.25 mg/kgChemotherapy
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 ± 18.02-5.72 ± 16.04
SecondaryChange 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).

Time frame:
Baseline and week 12
Reported as:
Mean · score on a scale
Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
score on a scaleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)-1.8 ± 16.6-5.3 ± 14.5
SecondaryNumber 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.

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)
Reported as:
Number · participants
Number of Participants With Treatment Emergent Adverse Events
participantsEnfortumab Vedotin 1.25 mg/kgChemotherapy
Number of Participants With Treatment Emergent Adverse Events290288
SecondaryNumber 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. 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.

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)
Reported as:
Number · participants
Number of Participants With ECOG Performance Status
participantsEnfortumab Vedotin 1.25 mg/kgChemotherapy
ECOG PS = 03457
ECOG PS = 1110118
ECOG PS >14044

Adverse events

Collected over 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). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Enfortumab Vedotin130/296 (43.9%)138/296 (46.6%)284/296 (95.9%)
Chemotherapy161/291 (55.3%)128/291 (44%)266/291 (91.4%)
Most frequent serious events
Showing 10 of 190
Most frequent serious events
EventEnfortumab VedotinChemotherapy
Acute kidney injuryRenal and urinary disorders19/2967/291
Febrile neutropeniaBlood and lymphatic system disorders4/29616/291
PneumoniaInfections and infestations12/2967/291
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)12/2967/291
PyrexiaGeneral disorders6/2969/291
Urinary tract infection bacterialInfections and infestations9/2963/291
NeutropeniaBlood and lymphatic system disorders4/2968/291
DiarrhoeaGastrointestinal disorders7/2964/291
Urinary tract infectionInfections and infestations7/2966/291
AnaemiaBlood and lymphatic system disorders4/2966/291
Most frequent other events
Showing 10 of 57
Most frequent other events
EventEnfortumab VedotinChemotherapy
AlopeciaSkin and subcutaneous tissue disorders139/296110/291
Decreased appetiteMetabolism and nutrition disorders119/29678/291
FatigueGeneral disorders107/29677/291
Peripheral sensory neuropathyNervous system disorders102/29666/291
PruritusSkin and subcutaneous tissue disorders102/29620/291
DiarrhoeaGastrointestinal disorders98/29664/291
NauseaGastrointestinal disorders89/29673/291
AnaemiaBlood and lymphatic system disorders57/29683/291
ConstipationGastrointestinal disorders81/29672/291
DysgeusiaNervous system disorders74/29623/291

Baseline characteristics

The full analysis set (FAS) consisted of all participants who were randomized.

Age, Continuous
Age, Continuous(Years)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
Mean66.52 ± 9.1166.81 ± 9.9366.67 ± 9.53
Sex: Female, Male
Sex: Female, Male(Participants)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
Female6375138
Male238232470
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
Hispanic or Latino292453
Not Hispanic or Latino230238468
Unknown or Not Reported424587
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
American Indian or Alaska Native000
Asian97103200
Native Hawaiian or Other Pacific Islander011
Black or African American224
White159155314
More than one race000
Unknown or Not Reported434689
ECOG PS
ECOG PS(participants)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
ECOG PS=0120124244
ECOG PS=1181183364
Liver Metastasis
Liver Metastasis(participants)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
Liver Metastasis=No208212420
Liver Metastasis=Yes9395188
Region
Region(participants)Enfortumab Vedotin 1.25 mg/kgChemotherapyTotal
Western Europe126129255
United States434487
Rest of the World132134266
07

Study locations

158 sites
  • UCI Chao Family Comprehensive Cancer Center
    Orange, California 92868, United States
  • University of California
    Sacramento, California 95817, United States
  • Innovative Clinical Research
    Whittier, California 90606, United States
  • University of Colorado
    Denver, Colorado 80045, United States
  • Smilow Cancer Hospital at Yale-New Haven
    New Haven, Connecticut 06510, United States
  • Sylvester Comprehensive Cancer Center
    Miami, Florida 33136, United States
  • Florida Hospital
    Orlando, Florida 32804, United States
  • Rush University Medical Center
    Chicago, Illinois 60612, United States
  • Norton Cancer Institute
    Louisville, Kentucky 40207, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Nebraska Cancer Specialists
    Omaha, Nebraska 68130, United States
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • Long Island Jewish Medical Center
    Lake Success, New York 11042, United States
  • Sidney Kimmel Center for Prostate and Urologic Cancers
    New York, New York 10065, United States
  • Montefiore Medical Center
    The Bronx, New York 10467, United States
  • White Plains Hospital Center for Cancer Care - Oncology Site
    White Plains, New York 10601, United States
  • Toledo Clinic Cancer Center
    Toledo, Ohio 43623, United States
  • Providence Portland Med Center
    Portland, Oregon 97213, United States
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Fox Chase Cancer Center
    Philadelphia, Pennsylvania 19111, United States
  • Lifespan Rhode Island Hospital
    Providence, Rhode Island 02903, United States
  • Saint Francis Hospital
    Greenville, South Carolina 29607, United States
  • HOPE Cancer Center of East Texas
    Tyler, Texas 75701, United States
  • Benaroya Research Institute at Virginia Mason
    Seattle, Washington 98101, United States
  • Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • Site AR54001
    Buenos Aires, Argentina
  • Site AU61006
    Adelaide, Australia
  • Site AU61001
    Miranda, Australia
  • Site AU61004
    St Leonards, Australia
  • Site AU61002
    Sydney, Australia
  • Site AT43005
    Linz, Austria
  • Site AT43001
    Salzburg, Austria
  • Site AT43004
    Vienna, Austria
  • Site BE32011
    Aalst, Belgium
  • Site BE32007
    Brussels, Belgium
  • Site BE32013
    Brussels, Belgium
  • Site BE32010
    Charleroi, Belgium
  • Site BE32001
    Ghent, Belgium
  • Site BE32008
    Ghent, Belgium
  • Site BE32005
    Hasselt, Belgium
  • Site BE32003
    Leuven, Belgium
  • Site BE32009
    Liège, Belgium
  • Site CA15015
    Calgary, Canada
  • Site CA15012
    Edmonton, Canada
  • Site CA15014
    London, Canada
  • Site CA15002
    Montreal, Canada
  • Site CA15007
    Montreal, Canada
  • Site CA15011
    Oshawa, Canada
  • Site CA15004
    Québec, Canada
  • Site CA15008
    Saskatoon, Canada
  • Site CA15001
    Sherbrooke, Canada
  • Site CA15005
    Toronto, Canada
  • Site CA15013
    Vancouver, Canada
  • Site DK45003
    Aalborg, Denmark
  • Site DK45004
    Copenhagen, Denmark
  • Site DK45001
    Herlev, Denmark
  • Site FR33021
    Besançon, France
  • Site FR33009
    Bordeaux, France
  • Site FR33018
    Bordeaux, France
  • Site FR33001
    Brest, France
  • Site FR33016
    Caen, France
  • Site FR33015
    Lyon, France
  • Site FR33014
    Marseille, France
  • Site FR33003
    Nice, France
  • Site FR33022
    Paris, France
  • Site FR33005
    Pierre-Bénite, France
  • Site FR33004
    Saint-Mandé, France
  • Site FR33002
    Strasbourg, France
  • Site FR33019
    Toulouse, France
  • Site FR33006
    Villejuif, France
  • Site DE49011
    Essen, Germany
  • Site DE49008
    Heidelberg, Germany
  • Site DE49010
    Münster, Germany
  • Site DE49003
    Tübingen, Germany
  • Site DE49009
    Würzburg, Germany
  • Site IT39008
    Arezzo, Italy
  • Site IT39019
    Cremona, Italy
  • Site IT39010
    Milan, Italy
  • Site IT39025
    Modena, Italy
  • Site IT39013
    Pisa, Italy
  • Site IT39014
    Reggio Emilia, Italy
  • Site IT39004
    Terni, Italy
  • Site JP81010
    Hirosaki, Aomori, Japan
  • Site JP81014
    Kashiwa, Chiba, Japan
  • Site JP81007
    Sapporo, Hokkaido, Japan
  • Site JP81026
    Sapporo, Hokkaido, Japan
  • Site JP81020
    Tsukuba, Ibaraki, Japan
  • Site JP81018
    Morioka, Iwate, Japan
  • Site JP81009
    Kita-gun, Kagawa-ken, Japan
  • Site JP81002
    Yokohama, Kanagawa, Japan
  • Site JP81005
    Sendai, Miyagi, Japan
  • Site JP81016
    Sayama, Osaka, Japan
  • Site JP81024
    Takatsuki, Osaka, Japan
  • Site JP81008
    Bunkyo-ku, Tokyo, Japan
  • Site JP81012
    Koto-ku, Tokyo, Japan
  • Site JP81013
    Shinjuku-ku, Tokyo, Japan
  • Site JP81011
    Ube, Yamaguchi, Japan
  • Site JP81015
    Chiba, Japan
  • Site JP81019
    Fukuoka, Japan
  • Site JP81023
    Fukuoka, Japan

Showing the first 100 of 158 sites across 19 countries.

08

References and documents

Publications

  • Rosenberg JE, Mamtani R, Sonpavde GP, Loriot Y, Duran I, Lee JL, Matsubara N, Vulsteke C, Castellano D, Sridhar SS, Pappot H, Gurney H, Bedke J, van der Heijden MS, Galli L, Keam B, Masumori N, Meran J, O'Donnell PH, Park SH, Grande E, Sengelov L, Uemura H, Skaltsa K, Campbell M, Matsangou M, Wu C, Hepp Z, McKay C, Powles T, Petrylak DP. Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy. Eur Urol. 2024 Jun;85(6):574-585. doi: 10.1016/j.eururo.2024.01.007. Epub 2024 Feb 28. PubMed 38418343 ↗
  • 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. PubMed 33577729 ↗

Study documents

  • Study protocol · Sep 14, 2020
  • Statistical analysis plan · Aug 10, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Supporting information: Study protocol, Sap, Csr

09

Registry details

Key details

Study ID
NCT03474107
Lead sponsor
Astellas Pharma Global Development, Inc.
Collaborators
Seagen Inc.
Responsible party
Sponsor
First posted
Mar 22, 2018
Start date
Jun 27, 2018
Primary completion
Jul 15, 2020
Completion
Nov 27, 2025
Results posted
Aug 24, 2021
Last update
Jan 9, 2026

Study contacts

Medical Director
study director · Astellas Pharma Global Development, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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