Study NCT03474107
A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
Submitted Date:  July 7, 2021 (v72)
Quality Control Review Has Not Concluded

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Open or close this module Study Identification
Unique Protocol ID: 7465-CL-0301
Brief Title: A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
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)
Secondary IDs: 2017-003344-21 [EudraCT Number]
Open or close this module Study Status
Record Verification: June 2021
Overall Status: Active, not recruiting
Study Start: June 27, 2018
Primary Completion: July 15, 2020 [Actual]
Study Completion: February 28, 2022 [Anticipated]
First Submitted: March 16, 2018
First Submitted that
Met QC Criteria:
March 16, 2018
First Posted: March 22, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: July 29, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Astellas Pharma Global Development, Inc.
Responsible Party: Sponsor
Collaborators: Seagen Inc.
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

The purpose of this study was to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy.

This study compared progression-free survival on study therapy (PFS1); the overall response rate (ORR) and the disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of participants treated with EV to participants treated with chemotherapy.

In addition, this study evaluated the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy and assessed the safety and tolerability of EV, as well as, the quality of life (QOL) and Patient Reported Outcomes (PRO) parameters.

Detailed Description: Participants considered an adult according to local regulation at the time of obtaining informed consent participated in the study. Sites in Japan Only: In case that EV is approved for marketing in Japan, the study will continue as "Phase 4 post-marketing study" in accordance with Good Post-marketing Study Practice after marketing authorization based on the indication approved. In this case, "Study" in the protocol is read as "Post-marketing study."
Open or close this module Conditions
Conditions: Ureteral Cancer
Urothelial Cancer
Bladder Cancer
Keywords: antibody drug conjugate
enfortumab vedotin (EV)
ASG-22ME
ASG-22CE
urothelial cancer
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 608 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Arm A: Enfortumab Vedotin 1.25 mg/kg
Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
Drug: Enfortumab Vedotin
Intravenous infusion
Other Names:
  • ASG-22ME
  • ASG-22CE
Active Comparator: Arm B: Chemotherapy
Participants received either 75 milligrams per square meter (mg/m^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
Drug: Docetaxel
Intravenous infusion
Drug: Vinflunine
Intravenous infusion
Drug: Paclitaxel
Intravenous infusion
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Overall Survival (OS)
[ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]

OS was defined as the time from the date of randomization until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier.
Secondary Outcome Measures:
1. Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
[ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]

PFS: time from date of randomization until date of documented radiological disease progression (PD) per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last radiological assessment (RA)/ date of randomization if no post-baseline RA was available. Participants who received any further anticancer therapy (ACT) for disease before radiological progression was censored at date of last RA before ACT started and participants who had PD/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow-up for PFS was based on data cut-off & is same as median follow-up time for OS.
2. Overall Response Rate (ORR) as Per RECIST V1.1
[ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. ORR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for ORR was based on data cut-off and is same as median follow-up time for OS.
3. Disease Control Rate (DCR) as Per RECIST V1.1
[ Time Frame: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]

DCR was defined as the percentage of participants with a CR, PR or a stable disease (SD) based on RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. Progressive disease is defined in PFS1 endpoint. DCR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for DCR was based on data cut-off and is same as median follow-up time for OS.
4. Duration of Response (DOR) as Per RECIST V1.1
[ Time Frame: From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ]

DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by investigator to the date of documented PD or death due to any cause whichever occurred first. If a participant has neither progressed nor died, the participant was censored at the date of last RA or at the date of first CR/PR if no subsequent post-baseline RA was available. Participants who received any further ACT for the disease before radiological progression were censored at the date of the last RA before the ACT started. In addition, participants who had PD/death after >= 2 missed RAs were censored at the last RA prior to the 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow up for DOR was based on data cut-off and is same as median follow-up time for OS. CR/PR and PD were defined in ORR and PFS1 endpoints, respectively.
5. Change From Baseline to Week 12 in European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Global Health Status (QL2 Score)
[ Time Frame: Baseline and week 12 ]

EORTC QLQ-C30 is a generic questionnaire consisting of 30 items. The instrument yields functional scales (physical, role, emotional, cognitive, social), symptom scales/items (fatigue, Nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), global health status, and financial impact score. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). The recall period for each question is "during the past week". All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Higher scores on the global health status and functioning scales indicate better health status/function.
6. Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
[ Time Frame: Baseline and week 12 ]

EQ-5D-5L is a health status instrument for self-reported assessment of 5 domains of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain is rated by selecting 1 of 5 standardized categorizations ranging from no problem to extreme problem. The final question is a visual analogue scale (VAS) to rank health status from 0 (best health imaginable) to 100 (worst health imaginable).
7. Number of Participants With Treatment Emergent Adverse Events
[ Time Frame: From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group) ]

An AE is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE is defined as an AE observed or worsened after starting administration of the study drug.
8. Number of Participants With ECOG Performance Status
[ Time Frame: End of treatment (EOT) (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group) ]

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

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
  2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
  3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
  4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
  5. Dead. Number of participants with ECOG PS was reported.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Subject is legally an adult according to local regulation at the time of signing informed consent.
  • Subject has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.
  • Subject must have experienced radiographic progression or relapse during or after a checkpoint inhibitor (CPI) (anti-programmed cell death protein 1 (PD1) or anti-programmed death-ligand 1 (PD-L1)) for locally advanced or metastatic disease. Subjects who discontinued CPI treatment due to toxicity are eligible provided that the subjects have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Subjects for whom the most recent therapy has been a non-CPI based regimen are eligible if the subjects have progressed/relapsed during or after the subjects most recent therapy. Locally advanced disease must not be amenable to resection with curative intent per the treating physician.
  • Subject must have received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting subject must have progressed within 12 months of completion.
  • Subject has radiologically documented metastatic or locally advanced disease at baseline.
  • An archival tumor tissue sample should be available for submission to central laboratory prior to study treatment. If an archival tumor tissue sample is not available, a fresh tissue sample should be provided. If a fresh tissue sample cannot be provided due to safety concerns, enrollment into the study must be discussed with the medical monitor.
  • Subject has ECOG PS of 0 or 1
  • The subject has the following baseline laboratory data:
    • absolute neutrophil count (ANC) ≥ 1500/mm3
    • platelet count ≥ 100 × 109/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 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, has not started a new systemic anticancer treatment and is still participating in the follow up phase of the study.

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.
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Astellas Pharma Global Development, Inc.
Locations: United States, California
UCI Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
University of California
Sacramento, California, United States, 95817
Innovative Clinical Research
Whittier, California, United States, 90606
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80045
United States, Connecticut
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, United States, 06510
United States, Florida
Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Florida Hospital
Orlando, Florida, United States, 32804
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40207
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Nebraska
Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68130
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Long Island Jewish Medical Center
Lake Success, New York, United States, 11042
Sidney Kimmel Center for Prostate and Urologic Cancers
New York, New York, United States, 10065
White Plains Hospital Center for Cancer Care - Oncology Site
White Plains, New York, United States, 10601
United States, Ohio
Toledo Clinic Cancer Center
Toledo, Ohio, United States, 43623
United States, Oregon
Providence Portland Med Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Rhode Island
Lifespan Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, South Carolina
Saint Francis Hospital
Greenville, South Carolina, United States, 29607
United States, Texas
HOPE Cancer Center of East Texas
Tyler, Texas, United States, 75701
United States, Washington
Benaroya Research Institute at Virginia Mason
Seattle, Washington, United States, 98101
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Argentina
Site AR54001
Buenos Aires, Argentina
Australia
Site AU61006
Adelaide, Australia
Site AU61001
Miranda, Australia
Site AU61004
St. Leonards, Australia
Site AU61002
Sydney, Australia
Austria
Site AT43005
Linz, Austria
Site AT43001
Salzburg, Austria
Site AT43004
Wien, Austria
Belgium
Site BE32011
Aalst, Belgium
Site BE32007
Brussels, Belgium
Site BE32013
Brussels, Belgium
Site BE32010
Charleroi, Belgium
Site BE32001
Gent, Belgium
Site BE32008
Gent, Belgium
Site BE32005
Hasselt, Belgium
Site BE32003
Leuven, Belgium
Site BE32009
Liège, Belgium
Canada
Site CA15015
Calgary, Canada
Site CA15012
Edmonton, Canada
Site CA15014
London, Canada
Site CA15007
Montreal, Canada
Site CA15011
Oshawa, Canada
Site CA15002
Quebec, Canada
Site CA15004
Quebec, Canada
Site CA15008
Saskatoon, Canada
Site CA15001
Sherbrooke, Canada
Site CA15005
Toronto, Canada
Site CA15013
Vancouver, Canada
Denmark
Site DK45003
Aalborg, Denmark
Site DK45004
Copenhagen, Denmark
Site DK45001
Herlev, Denmark
France
Site FR33021
Besancon, France
Site FR33009
Bordeaux, France
Site FR33018
Bordeaux, France
Site FR33001
Brest, France
Site FR33016
Caen, France
Site FR33015
Lyon, France
Site FR33014
Marseille, France
Site FR33003
Nice, France
Site FR33022
Paris, France
Site FR33005
Pierre-Bénite, France
Site FR33004
Saint-Mande, France
Site FR33002
Strasbourg, France
Site FR33019
Toulouse, France
Site FR33006
Villejuif, France
Germany
Site DE49011
Essen, Germany
Site DE49008
Heidelberg, Germany
Site DE49010
Munster, Germany
Site DE49003
Tübingen, Germany
Site DE49009
Würzburg, Germany
Italy
Site IT39008
Arezzo, Italy
Site IT39019
Cremona, Italy
Site IT39010
Milan, Italy
Site IT39025
Modena, Italy
Site IT39013
Pisa, Italy
Site IT39014
Reggio Emilia, Italy
Site IT39004
Terni, Italy
Japan
Site JP81015
Chiba, Japan
Site JP81019
Fukuoka, Japan
Site JP81023
Fukuoka, Japan
Site JP81004
Hiroshima, Japan
Site JP81001
Kyoto, Japan
Site JP81017
Niigata, Japan
Site JP81003
Okayama, Japan
Site JP81022
Osaka, Japan
Site JP81021
Tokushima, Japan
Site JP81006
Toyama, Japan
Japan, Aomori
Site JP81010
Hirosaki, Aomori, Japan
Japan, Chiba
Site JP81014
Kashiwa, Chiba, Japan
Japan, Hokkaido
Site JP81007
Sapporo, Hokkaido, Japan
Site JP81026
Sapporo, Hokkaido, Japan
Japan, Ibaraki
Site JP81020
Tsukuba, Ibaraki, Japan
Japan, Iwate
Site JP81018
Morioka, Iwate, Japan
Japan, Kagawa
Site JP81009
Kita-gun, Kagawa, Japan
Japan, Kanagawa
Site JP81002
Yokohama, Kanagawa, Japan
Japan, Miyagi
Site JP81005
Sendai, Miyagi, Japan
Japan, Osaka
Site JP81016
Osakasayama, Osaka, Japan
Site JP81024
Takatsuki, Osaka, Japan
Japan, Tokyo
Site JP81008
Bunkyo-ku, Tokyo, Japan
Site JP81012
Koto-ku, Tokyo, Japan
Site JP81013
Shinjuku-ku, Tokyo, Japan
Japan, Yamaguchi
Site JP81011
Ube, Yamaguchi, Japan
Korea, Republic of
Site KR82006
Daejeon, Korea, Republic of
Site KR82007
Goyang-Si, Korea, Republic of
Site KR82012
Hwasun-gun, Korea, Republic of
Site KR82002
Incheon, Korea, Republic of
Site KR82001
Seongnam-si, Korea, Republic of
Site KR82003
Seoul, Korea, Republic of
Site KR82004
Seoul, Korea, Republic of
Site KR82008
Seoul, Korea, Republic of
Site KR82009
Seoul, Korea, Republic of
Site KR82010
Seoul, Korea, Republic of
Site KR82005
Shin, Korea, Republic of
Netherlands
Site NL31002
Amsterdam, Netherlands
Site NL31003
Amsterdam, Netherlands
Site NL31009
Nijmegen, Netherlands
Site NL31001
Tilburg, Netherlands
Portugal
Site PT35105
Lisboa, Portugal
Site PT35102
Lisbon, Portugal
Site PT35106
Porto, Portugal
Russian Federation
Site RU70002
Ivanovo, Russian Federation
Site RU70009
Obninsk, Russian Federation
Site RU70005
Omsk, Russian Federation
Site RU70015
Vologda, Russian Federation
Spain
Site ES34010
Badajoz, Spain
Site ES34002
Badalona, Spain
Site ES34001
Barcelona, Spain
Site ES34012
Barcelona, Spain
Site ES34023
Barcelona, Spain
Site ES34014
Córdoba, Spain
Site ES34003
Madrid, Spain
Site ES34013
Madrid, Spain
Site ES34015
Madrid, Spain
Site ES34017
Madrid, Spain
Site ES34011
Manresa, Spain
Site ES34019
Pamplona, Spain
Site ES34005
Seville, Spain
Site ES34007
Valencia, Spain
Site ES34008
Valencia, Spain
Switzerland
Site CH41002
Bern, Switzerland
Site CH41001
Chur, Switzerland
Taiwan
Site TW88602
Kaohsiung, Taiwan
Site TW88605
Kaohsiung, Taiwan
Site TW88606
Taichung, Taiwan
Site TW88601
Tainan, Taiwan
Site TW88604
Taipei, Taiwan
Site TW88607
Taoyuan, Taiwan
United Kingdom
Site GB44005
London, United Kingdom
Site GB44006
London, United Kingdom
Site GB44002
Sheffield, United Kingdom
Site GB44011
Southampton, United Kingdom
Site GB44013
Sutton, United Kingdom
Site GB44004
Wirral, United Kingdom
Open or close this module IPDSharing
Plan to Share IPD: 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 compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame:
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria:
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: September 14, 2020
Uploaded: 07/07/2021 05:18
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: August 10, 2020
Uploaded: 07/07/2021 05:18
File Name: SAP_001.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details 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.
Pre-assignment Details 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).
 
Arm/Group Title Enfortumab Vedotin 1.25mg/kg Chemotherapy
Arm/Group Description 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. 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.
Period Title: Overall Study
Started 301 307
Treated 296 291
Completed 56 [1] 22 [1]
Not Completed 245 285
Reason Not Completed
Adverse Event 42 46
Death 2 2
Lost to Follow-up 0 1
Progressive Disease 177 180
Protocol Violation 1 1
Withdrawal by Subject 15 27
Physician Decision 7 22
Miscellaneous 1 6
[1]Participants still on treatment as of data cut-off date 15-Jul-2020
Open or close this module Baseline Characteristics
   
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapyTotal
Arm/Group DescriptionParticipants 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.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 of all reporting groups
Overall Number of Baseline Participants 301 307 608
Baseline Analysis Population Description
Age, Continuous
Mean (Standard Deviation)
Unit of measure: Years
Number Analyzed301 Participants307 Participants608 Participants
66.52(9.11)66.81(9.93)66.67(9.53)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed301 Participants307 Participants608 Participants
Female63 20.93%75 24.43%138 22.7%
Male238 79.07%232 75.57%470 77.3%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed301 Participants307 Participants608 Participants
Hispanic or Latino29 9.63%24 7.82%53 8.72%
Not Hispanic or Latino230 76.41%238 77.52%468 76.97%
Unknown or Not Reported42 13.95%45 14.66%87 14.31%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed301 Participants307 Participants608 Participants
American Indian or Alaska Native0 0%0 0%0 0%
Asian97 32.23%103 33.55%200 32.89%
Native Hawaiian or Other Pacific Islander0 0%1 0.33%1 0.16%
Black or African American2 0.66%2 0.65%4 0.66%
White159 52.82%155 50.49%314 51.64%
More than one race0 0%0 0%0 0%
Unknown or Not Reported43 14.29%46 14.98%89 14.64%
ECOG PS [1]
Measure Type: Number
Unit of measure: participants
Number Analyzed301 Participants307 Participants608 Participants
ECOG PS=0
120124244
ECOG PS=1
181183364
 
[1]Measure Description: 

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

  1. Restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature
  2. Ambulatory & capable of all self-care but unable to carry out any work activities.Up & 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 Participants were categorized based on ECOG PS 0 or 1
Liver Metastasis [1]
Measure Type: Number
Unit of measure: participants
Number Analyzed301 Participants307 Participants608 Participants
Liver Metastasis=No
208212420
Liver Metastasis=Yes
9395188
 
[1]Measure Description: Participants were categorized based on liver metastasis (yes or no).
Region [1]
Measure Type: Number
Unit of measure: participants
Number Analyzed301 Participants307 Participants608 Participants
Western Europe
126129255
United States
434487
Rest of the World
132134266
 
[1]Measure Description: Participants were categorized based on region western europe, US and rest of the world.
Open or close this module Outcome Measures
1. Primary Outcome:
Title Overall Survival (OS)
Description 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)
Outcome Measure Data
Analysis Population Description
FAS Population
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed301 307
Median (95% Confidence Interval)
Unit of Measure: months
12.88 (10.58 to 15.21) 8.97 (8.05 to 10.74)
Statistical Analysis 1
Statistical Analysis OverviewComparison GroupsEnfortumab Vedotin 1.25 mg/kg, Chemotherapy
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value0.00142
CommentsStratification 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.
MethodStratified Log rank
Comments[Not specified]
Method of EstimationEstimation ParameterStratified Hazard Ratio
Estimated Value0.702
Confidence Interval(2-sided) 95%
0.556 to 0.886
Estimation CommentsCox proportional hazards model with treatment, ECOG PS, geographic region and liver metastasis as the explanatory variables.
2. Secondary Outcome:
Title Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Description 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)
Outcome Measure Data
Analysis Population Description
FAS Population
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed301 307
Median (95% Confidence Interval)
Unit of Measure: months
5.55 (5.32 to 5.82) 3.71 (3.52 to 3.94)
Statistical Analysis 1
Statistical Analysis OverviewComparison GroupsEnfortumab Vedotin 1.25 mg/kg, Chemotherapy
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.00001
CommentsStratification 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.
MethodStratified Log Rank
Comments[Not specified]
Method of EstimationEstimation ParameterStratified Hazard Ratio
Estimated Value0.615
Confidence Interval(2-sided) 95%
0.505 to 0.748
Estimation CommentsCox proportional hazards model with treatment, ECOG PS, geographic region and liver metastasis as the explanatory variables.
3. Secondary Outcome:
Title Overall Response Rate (ORR) as Per RECIST V1.1
Description 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)
Outcome Measure Data
Analysis Population Description
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.
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed288 296
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40.6 (34.90 to 46.54) 17.9 (13.71 to 22.76)
Statistical Analysis 1
Statistical Analysis OverviewComparison GroupsEnfortumab Vedotin 1.25 mg/kg, Chemotherapy
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.001
Comments"Stratification factors were ECOG PS, Region and Liver Metastasis.
MethodStratified Cochran-Mantel-Haenszel
Comments[Not specified]
4. Secondary Outcome:
Title Disease Control Rate (DCR) as Per RECIST V1.1
Description 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)
Outcome Measure Data
Analysis Population Description
RES Population
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed288 296
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
71.9 (66.30 to 76.99) 53.4 (47.52 to 59.17)
Statistical Analysis 1
Statistical Analysis OverviewComparison GroupsEnfortumab Vedotin 1.25 mg/kg, Chemotherapy
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.001
CommentsStratification factors were ECOG PS, Region and Liver Metastasis.
MethodStratified Cochran-Mantel-Haenszel
Comments[Not specified]
5. Secondary Outcome:
Title Duration of Response (DOR) as Per RECIST V1.1
Description 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)
Outcome Measure Data
Analysis Population Description
RES population with available data.
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed117 53
Median (95% Confidence Interval)
Unit of Measure: months
7.39 (5.59 to 9.46) 8.11 (5.65 to 9.56)
6. Secondary Outcome:
Title 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)
Description 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
Outcome Measure Data
Analysis Population Description
FAS population with available data.
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed127 102
Mean (Standard Deviation)
Unit of Measure: score on a scale
-2.30 (18.02) -5.72 (16.04)
7. Secondary Outcome:
Title Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
Description 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
Outcome Measure Data
Analysis Population Description
FAS population with available data.
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed124 102
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.8 (16.6) -5.3 (14.5)
8. Secondary Outcome:
Title Number of Participants With Treatment Emergent Adverse Events
Description 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)
Outcome Measure Data
Analysis Population Description
The safety analysis set (SAF) consisted of all participants who received any amount of study drug, and was used for safety analyses.
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed296 291
Measure Type: Number
Unit of Measure: participants
290 97.97% 288 98.97%
9. Secondary Outcome:
Title Number of Participants With ECOG Performance Status
Description

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)
Outcome Measure Data
Analysis Population Description
Safety Population
 
Arm/Group TitleEnfortumab Vedotin 1.25 mg/kgChemotherapy
Arm/Group DescriptionParticipants 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.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 Number of Participants Analyzed296 291
Measure Type: Number
Unit of Measure: participants
ECOG PS = 0
34 11.49% 57 19.59%
ECOG PS = 1
110 37.16% 118 40.55%
ECOG PS = >1
40 13.51% 44 15.12%

Quality Control Review Comment provided by the National Library of Medicine:

  1. Required information appears to be missing.
Open or close this module Adverse Events
 
Time Frame From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)
Adverse Event Reporting Description [Not specified]
 
Arm/Group Title Enfortumab Vedotin Chemotherapy
Arm/Group Description 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. 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.
All-Cause Mortality
  Enfortumab VedotinChemotherapy
 Affected/At Risk (%)# Events Affected/At Risk (%)# Events
Total 130 / 296 (43.92%)161 / 291 (55.33%)
Serious Adverse Events
  Enfortumab VedotinChemotherapy
 Affected/At Risk (%)# Events Affected/At Risk (%)# Events
Total 138 / 296 (46.62%)128 / 291 (43.99%)
Blood and lymphatic system disorders
Anaemia A∗ 4 / 296 (1.35%)46 / 291 (2.06%)7
Bone marrow failure A∗ 0 / 296 (0%)02 / 291 (0.69%)4
Febrile neutropenia A∗ 4 / 296 (1.35%)416 / 291 (5.5%)16
Leukopenia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Neutropenia A∗ 4 / 296 (1.35%)48 / 291 (2.75%)9
Pancytopenia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Thrombocytopenia A∗ 2 / 296 (0.68%)20 / 291 (0%)0
Cardiac disorders
Angina pectoris A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Atrial fibrillation A∗ 5 / 296 (1.69%)51 / 291 (0.34%)1
Atrial flutter A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Bradycardia A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Cardiac arrest A∗ 0 / 296 (0%)02 / 291 (0.69%)2
Cardiac failure A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Cardiogenic shock A∗ 0 / 296 (0%)01 / 291 (0.34%)2
Myocardial infarction A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Palpitations A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Sinus tachycardia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Ventricular hypokinesia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Ear and labyrinth disorders
Deafness neurosensory A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Vertigo A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Endocrine disorders
Adrenal insufficiency A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Inappropriate antidiuretic hormone secretion A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Eye disorders
Blepharitis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Cataract A∗ 2 / 296 (0.68%)50 / 291 (0%)0
Gastrointestinal disorders
Abdominal pain A∗ 3 / 296 (1.01%)36 / 291 (2.06%)6
Abdominal pain lower A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Abdominal pain upper A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Ascites A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Colitis A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Colonic fistula A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Constipation A∗ 2 / 296 (0.68%)23 / 291 (1.03%)3
Diarrhoea A∗ 7 / 296 (2.36%)84 / 291 (1.37%)6
Duodenal obstruction A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Fistula of small intestine A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Gastrointestinal haemorrhage A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Haemorrhagic ascites A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Ileus A∗ 1 / 296 (0.34%)12 / 291 (0.69%)2
Intestinal obstruction A∗ 0 / 296 (0%)02 / 291 (0.69%)3
Nausea A∗ 2 / 296 (0.68%)22 / 291 (0.69%)2
Oesophagitis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Rectal haemorrhage A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Small intestinal obstruction A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Upper gastrointestinal haemorrhage A∗ 0 / 296 (0%)02 / 291 (0.69%)2
Vomiting A∗ 5 / 296 (1.69%)51 / 291 (0.34%)1
General disorders
Asthenia A∗ 3 / 296 (1.01%)31 / 291 (0.34%)1
Chest pain A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Chills A∗ 2 / 296 (0.68%)21 / 291 (0.34%)1
Death A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Extravasation A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Fatigue A∗ 3 / 296 (1.01%)42 / 291 (0.69%)2
General physical health deterioration A∗ 2 / 296 (0.68%)35 / 291 (1.72%)5
Malaise A∗ 2 / 296 (0.68%)23 / 291 (1.03%)4
Mucosal inflammation A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Multiple organ dysfunction syndrome A∗ 3 / 296 (1.01%)30 / 291 (0%)0
Non-cardiac chest pain A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Oedema peripheral A∗ 2 / 296 (0.68%)21 / 291 (0.34%)1
Pyrexia A∗ 6 / 296 (2.03%)69 / 291 (3.09%)11
Systemic inflammatory response syndrome A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Hepatobiliary disorders
Cholangitis A∗ 1 / 296 (0.34%)20 / 291 (0%)0
Cholecystitis acute A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Hepatic function abnormal A∗ 2 / 296 (0.68%)41 / 291 (0.34%)2
Liver disorder A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Immune system disorders
Hypersensitivity A∗ 2 / 296 (0.68%)20 / 291 (0%)0
Infections and infestations
Abscess bacterial A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Appendicitis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Bacteraemia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Bronchitis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Cellulitis A∗ 3 / 296 (1.01%)32 / 291 (0.69%)4
Clostridium difficile colitis A∗ 0 / 296 (0%)01 / 291 (0.34%)2
Conjunctivitis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Device related infection A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Device related sepsis A∗ 1 / 296 (0.34%)20 / 291 (0%)0
Escherichia pyelonephritis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Escherichia urinary tract infection A∗ 3 / 296 (1.01%)41 / 291 (0.34%)1
Febrile infection A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Gastroenteritis A∗ 0 / 296 (0%)01 / 291 (0.34%)2
Infected skin ulcer A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Infection A∗ 2 / 296 (0.68%)20 / 291 (0%)0
Infective spondylitis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Neutropenic sepsis A∗ 0 / 296 (0%)01 / 291 (0.34%)2
Pelvic abscess A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Pleural infection A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Pneumocystis jirovecii pneumonia A∗ 0 / 296 (0%)02 / 291 (0.69%)5
Pneumonia A∗ 12 / 296 (4.05%)147 / 291 (2.41%)9
Pneumonia klebsiella A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Pneumonia legionella A∗ 0 / 296 (0%)01 / 291 (0.34%)3
Pneumonia pneumococcal A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Pneumonia viral A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Pyelonephritis A∗ 0 / 296 (0%)02 / 291 (0.69%)5
Pyelonephritis acute A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Sepsis A∗ 5 / 296 (1.69%)63 / 291 (1.03%)5
Septic shock A∗ 4 / 296 (1.35%)61 / 291 (0.34%)2
Staphylococcal bacteraemia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Staphylococcal sepsis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Streptococcal urinary tract infection A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Urinary tract infection A∗ 7 / 296 (2.36%)76 / 291 (2.06%)7
Urinary tract infection bacterial A∗ 9 / 296 (3.04%)103 / 291 (1.03%)3
Urinary tract infection enterococcal A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Urosepsis A∗ 2 / 296 (0.68%)26 / 291 (2.06%)7
Injury, poisoning and procedural complications
Ankle fracture A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Fall A∗ 2 / 296 (0.68%)21 / 291 (0.34%)1
Infusion related reaction A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Radius fracture A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Reactive gastropathy A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Toxicity to various agents A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Investigations
Blood creatinine increased A∗ 0 / 296 (0%)01 / 291 (0.34%)1
C-reactive protein increased A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Gamma-glutamyltransferase increased A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Hepatic enzyme increased A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Neutrophil count decreased A∗ 2 / 296 (0.68%)35 / 291 (1.72%)6
Platelet count decreased A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Metabolism and nutrition disorders
Decreased appetite A∗ 5 / 296 (1.69%)51 / 291 (0.34%)1
Dehydration A∗ 2 / 296 (0.68%)24 / 291 (1.37%)4
Hypercalcaemia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Hyperglycaemia A∗ 4 / 296 (1.35%)51 / 291 (0.34%)1
Hyperkalaemia A∗ 1 / 296 (0.34%)14 / 291 (1.37%)4
Hypernatraemia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Hypoglycaemia A∗ 1 / 296 (0.34%)12 / 291 (0.69%)2
Hyponatraemia A∗ 2 / 296 (0.68%)23 / 291 (1.03%)3
Hypophagia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Hypovolaemia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Metabolic acidosis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Type 2 diabetes mellitus A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Musculoskeletal and connective tissue disorders
Back pain A∗ 2 / 296 (0.68%)23 / 291 (1.03%)3
Bone pain A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Lumbar spinal stenosis A∗ 1 / 296 (0.34%)20 / 291 (0%)0
Muscular weakness A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Myalgia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Pain in extremity A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Pathological fracture A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Bladder transitional cell carcinoma A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Malignant neoplasm progression A∗ 12 / 296 (4.05%)157 / 291 (2.41%)7
Malignant pleural effusion A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Metastases to central nervous system A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Tumour associated fever A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Tumour haemorrhage A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Nervous system disorders
Brain oedema A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Cerebral haematoma A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Dementia A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Encephalopathy A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Frontotemporal dementia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Neuralgia A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Peripheral sensorimotor neuropathy A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Peripheral sensory neuropathy A∗ 2 / 296 (0.68%)21 / 291 (0.34%)1
Polyneuropathy A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Spinal cord compression A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Syncope A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Product Issues
Device occlusion A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Psychiatric disorders
Confusional state A∗ 2 / 296 (0.68%)22 / 291 (0.69%)2
Delirium A∗ 1 / 296 (0.34%)13 / 291 (1.03%)3
Renal and urinary disorders
Acute kidney injury A∗ 19 / 296 (6.42%)317 / 291 (2.41%)7
Azotaemia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Calculus bladder A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Choluria A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Cystitis noninfective A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Haematuria A∗ 5 / 296 (1.69%)63 / 291 (1.03%)3
Hydronephrosis A∗ 3 / 296 (1.01%)31 / 291 (0.34%)1
Renal impairment A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Urinary retention A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Urinary tract obstruction A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Reproductive system and breast disorders
Metrorrhagia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Aspiration A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Cough A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Dyspnoea A∗ 4 / 296 (1.35%)53 / 291 (1.03%)3
Hiccups A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Interstitial lung disease A∗ 0 / 296 (0%)02 / 291 (0.69%)2
Laryngospasm A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Organising pneumonia A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Pleural effusion A∗ 2 / 296 (0.68%)21 / 291 (0.34%)1
Pneumonitis A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Pulmonary embolism A∗ 2 / 296 (0.68%)20 / 291 (0%)0
Respiratory distress A∗ 0 / 296 (0%)01 / 291 (0.34%)2
Respiratory failure A∗ 1 / 296 (0.34%)21 / 291 (0.34%)1
Skin and subcutaneous tissue disorders
Blister A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Decubitus ulcer A∗ 1 / 296 (0.34%)11 / 291 (0.34%)1
Dermatitis bullous A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Drug eruption A∗ 2 / 296 (0.68%)50 / 291 (0%)0
Rash A∗ 3 / 296 (1.01%)30 / 291 (0%)0
Rash maculo-papular A∗ 4 / 296 (1.35%)40 / 291 (0%)0
Rash vesicular A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Toxic skin eruption A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Vascular disorders
Aortic aneurysm A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Deep vein thrombosis A∗ 0 / 296 (0%)02 / 291 (0.69%)2
Hypotension A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Iliac artery occlusion A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Vascular compression A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Vein disorder A∗ 0 / 296 (0%)01 / 291 (0.34%)1
Vena cava thrombosis A∗ 1 / 296 (0.34%)10 / 291 (0%)0
Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA v23.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  Enfortumab VedotinChemotherapy
 Affected/At Risk (%)# Events Affected/At Risk (%)# Events
Total 284 / 296 (95.95%)266 / 291 (91.41%)
Blood and lymphatic system disorders
Anaemia A∗ 57 / 296 (19.26%)9883 / 291 (28.52%)136
Neutropenia A∗ 16 / 296 (5.41%)3020 / 291 (6.87%)37
Eye disorders
Dry eye A∗ 19 / 296 (6.42%)243 / 291 (1.03%)3
Lacrimation increased A∗ 30 / 296 (10.14%)3712 / 291 (4.12%)15
Vision blurred A∗ 16 / 296 (5.41%)205 / 291 (1.72%)5
Gastrointestinal disorders
Abdominal pain A∗ 37 / 296 (12.5%)5224 / 291 (8.25%)33
Constipation A∗ 81 / 296 (27.36%)11672 / 291 (24.74%)105
Diarrhoea A∗ 98 / 296 (33.11%)17164 / 291 (21.99%)89
Dry mouth A∗ 24 / 296 (8.11%)267 / 291 (2.41%)7
Dyspepsia A∗ 19 / 296 (6.42%)229 / 291 (3.09%)10
Nausea A∗ 89 / 296 (30.07%)11973 / 291 (25.09%)92
Stomatitis A∗ 27 / 296 (9.12%)3519 / 291 (6.53%)27
Vomiting A∗ 38 / 296 (12.84%)5044 / 291 (15.12%)57
General disorders
Asthenia A∗ 43 / 296 (14.53%)8539 / 291 (13.4%)85
Chills A∗ 16 / 296 (5.41%)185 / 291 (1.72%)5
Fatigue A∗ 107 / 296 (36.15%)19777 / 291 (26.46%)121
Malaise A∗ 12 / 296 (4.05%)1319 / 291 (6.53%)24
Oedema peripheral A∗ 25 / 296 (8.45%)3239 / 291 (13.4%)46
Pyrexia A∗ 60 / 296 (20.27%)9933 / 291 (11.34%)47
Infections and infestations
Conjunctivitis A∗ 18 / 296 (6.08%)232 / 291 (0.69%)2
Nasopharyngitis A∗ 15 / 296 (5.07%)189 / 291 (3.09%)9
Urinary tract infection A∗ 21 / 296 (7.09%)2212 / 291 (4.12%)15
Injury, poisoning and procedural complications
Fall A∗ 15 / 296 (5.07%)198 / 291 (2.75%)8
Investigations
Alanine aminotransferase increased A∗ 27 / 296 (9.12%)454 / 291 (1.37%)5
Aspartate aminotransferase increased A∗ 36 / 296 (12.16%)565 / 291 (1.72%)7
Blood creatinine increased A∗ 26 / 296 (8.78%)386 / 291 (2.06%)6
Lymphocyte count decreased A∗ 12 / 296 (4.05%)3517 / 291 (5.84%)50
Neutrophil count decreased A∗ 32 / 296 (10.81%)7052 / 291 (17.87%)159
Weight decreased A∗ 47 / 296 (15.88%)7320 / 291 (6.87%)20
White blood cell count decreased A∗ 16 / 296 (5.41%)4532 / 291 (11%)97
Metabolism and nutrition disorders
Decreased appetite A∗ 119 / 296 (40.2%)15778 / 291 (26.8%)104
Hyperglycaemia A∗ 28 / 296 (9.46%)645 / 291 (1.72%)7
Hypokalaemia A∗ 19 / 296 (6.42%)2210 / 291 (3.44%)22
Hypomagnesaemia A∗ 18 / 296 (6.08%)288 / 291 (2.75%)9
Hyponatraemia A∗ 19 / 296 (6.42%)3610 / 291 (3.44%)13
Musculoskeletal and connective tissue disorders
Arthralgia A∗ 19 / 296 (6.42%)2336 / 291 (12.37%)44
Back pain A∗ 25 / 296 (8.45%)2823 / 291 (7.9%)25
Muscular weakness A∗ 15 / 296 (5.07%)237 / 291 (2.41%)8
Myalgia A∗ 15 / 296 (5.07%)2331 / 291 (10.65%)40
Pain in extremity A∗ 16 / 296 (5.41%)2013 / 291 (4.47%)19
Nervous system disorders
Dizziness A∗ 26 / 296 (8.78%)3416 / 291 (5.5%)18
Dysgeusia A∗ 74 / 296 (25%)9923 / 291 (7.9%)28
Headache A∗ 9 / 296 (3.04%)1017 / 291 (5.84%)22
Neuropathy peripheral A∗ 20 / 296 (6.76%)4516 / 291 (5.5%)20
Paraesthesia A∗ 15 / 296 (5.07%)238 / 291 (2.75%)10
Peripheral sensory neuropathy A∗ 102 / 296 (34.46%)30166 / 291 (22.68%)99
Psychiatric disorders
Insomnia A∗ 31 / 296 (10.47%)3223 / 291 (7.9%)25
Renal and urinary disorders
Haematuria A∗ 31 / 296 (10.47%)4122 / 291 (7.56%)28
Respiratory, thoracic and mediastinal disorders
Cough A∗ 24 / 296 (8.11%)2517 / 291 (5.84%)17
Dyspnoea A∗ 25 / 296 (8.45%)3126 / 291 (8.93%)36
Skin and subcutaneous tissue disorders
Alopecia A∗ 139 / 296 (46.96%)163110 / 291 (37.8%)121
Drug eruption A∗ 26 / 296 (8.78%)404 / 291 (1.37%)4
Dry skin A∗ 50 / 296 (16.89%)5711 / 291 (3.78%)11
Pruritus A∗ 102 / 296 (34.46%)15320 / 291 (6.87%)20
Rash A∗ 49 / 296 (16.55%)7716 / 291 (5.5%)16
Rash maculo-papular A∗ 49 / 296 (16.55%)996 / 291 (2.06%)6
Skin hyperpigmentation A∗ 19 / 296 (6.42%)201 / 291 (0.34%)2
Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA v23.0
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.
Results Point of Contact:
Name/Official Title:
Clinical Trial Disclosure
Organization:
Astellas Pharma Global Development, Inc.
Phone:
800-888-7704
Email:
astellas.resultsdisclosure@astellas.com

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