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

March 26, 2024 updated by: Astellas Pharma Global Development, Inc.

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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

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

Study Type

Interventional

Enrollment (Actual)

608

Phase

  • Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Site AR54001
  • Australia
      • Adelaide, Australia
        • Site AU61006
      • Miranda, Australia
        • Site AU61001
      • St. Leonards, Australia
        • Site AU61004
      • Sydney, Australia
        • Site AU61002
  • Austria
      • Linz, Austria
        • Site AT43005
      • Salzburg, Austria
        • Site AT43001
      • Wien, Austria
        • Site AT43004
  • Belgium
      • Aalst, Belgium
        • Site BE32011
      • Brussels, Belgium
        • Site BE32007
      • Brussels, Belgium
        • Site BE32013
      • Charleroi, Belgium
        • Site BE32010
      • Gent, Belgium
        • Site BE32001
      • Gent, Belgium
        • Site BE32008
      • Hasselt, Belgium
        • Site BE32005
      • Leuven, Belgium
        • Site BE32003
      • Liège, Belgium
        • Site BE32009
  • Canada
      • Calgary, Canada
        • Site CA15015
      • Edmonton, Canada
        • Site CA15012
      • London, Canada
        • Site CA15014
      • Montreal, Canada
        • Site CA15002
      • Montreal, Canada
        • Site CA15007
      • Oshawa, Canada
        • Site CA15011
      • Quebec, Canada
        • Site CA15004
      • Saskatoon, Canada
        • Site CA15008
      • Sherbrooke, Canada
        • Site CA15001
      • Toronto, Canada
        • Site CA15005
      • Vancouver, Canada
        • Site CA15013
  • Denmark
      • Aalborg, Denmark
        • Site DK45003
      • Copenhagen, Denmark
        • Site DK45004
      • Herlev, Denmark
        • Site DK45001
  • France
      • Besancon, France
        • Site FR33021
      • Bordeaux, France
        • Site FR33009
      • Bordeaux, France
        • Site FR33018
      • Brest, France
        • Site FR33001
      • Caen, France
        • Site FR33016
      • Lyon, France
        • Site FR33015
      • Marseille, France
        • Site FR33014
      • Nice, France
        • Site FR33003
      • Paris, France
        • Site FR33022
      • Pierre-Bénite, France
        • Site FR33005
      • Saint-Mande, France
        • Site FR33004
      • Strasbourg, France
        • Site FR33002
      • Toulouse, France
        • Site FR33019
      • Villejuif, France
        • Site FR33006
  • Germany
      • Essen, Germany
        • Site DE49011
      • Heidelberg, Germany
        • Site DE49008
      • Münster, Germany
        • Site DE49010
      • Tübingen, Germany
        • Site DE49003
      • Würzburg, Germany
        • Site DE49009
  • Italy
      • Arezzo, Italy
        • Site IT39008
      • Cremona, Italy
        • Site IT39019
      • Milan, Italy
        • Site IT39010
      • Modena, Italy
        • Site IT39025
      • Pisa, Italy
        • Site IT39013
      • Reggio Emilia, Italy
        • Site IT39014
      • Terni, Italy
        • Site IT39004
  • Japan
      • Chiba, Japan
        • Site JP81015
      • Fukuoka, Japan
        • Site JP81019
      • Fukuoka, Japan
        • Site JP81023
      • Hiroshima, Japan
        • Site JP81004
      • Kyoto, Japan
        • Site JP81001
      • Niigata, Japan
        • Site JP81017
      • Okayama, Japan
        • Site JP81003
      • Osaka, Japan
        • Site JP81022
      • Tokushima, Japan
        • Site JP81021
      • Toyama, Japan
        • Site JP81006
    • Aomori
      • Hirosaki, Aomori, Japan
        • Site JP81010
    • Chiba
      • Kashiwa, Chiba, Japan
        • Site JP81014
    • Hokkaido
      • Sapporo, Hokkaido, Japan
        • Site JP81007
      • Sapporo, Hokkaido, Japan
        • Site JP81026
    • Ibaraki
      • Tsukuba, Ibaraki, Japan
        • Site JP81020
    • Iwate
      • Morioka, Iwate, Japan
        • Site JP81018
    • Kagawa
      • Kita-gun, Kagawa, Japan
        • Site JP81009
    • Kanagawa
      • Yokohama, Kanagawa, Japan
        • Site JP81002
    • Miyagi
      • Sendai, Miyagi, Japan
        • Site JP81005
    • Osaka
      • Osakasayama, Osaka, Japan
        • Site JP81016
      • Takatsuki, Osaka, Japan
        • Site JP81024
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan
        • Site JP81008
      • Koto-ku, Tokyo, Japan
        • Site JP81012
      • Shinjuku-ku, Tokyo, Japan
        • Site JP81013
    • Yamaguchi
      • Ube, Yamaguchi, Japan
        • Site JP81011
  • Korea, Republic of
      • Daejeon, Korea, Republic of
        • Site KR82006
      • Goyang-Si, Korea, Republic of
        • Site KR82007
      • Hwasun-gun, Korea, Republic of
        • Site KR82012
      • Incheon, Korea, Republic of
        • Site KR82002
      • Seongnam-si, Korea, Republic of
        • Site KR82001
      • Seoul, Korea, Republic of
        • Site KR82010
      • Seoul, Korea, Republic of
        • Site KR82004
      • Seoul, Korea, Republic of
        • Site KR82003
      • Seoul, Korea, Republic of
        • Site KR82008
      • Seoul, Korea, Republic of
        • Site KR82009
      • Shin, Korea, Republic of
        • Site KR82005
  • Netherlands
      • Amsterdam, Netherlands
        • Site NL31002
      • Amsterdam, Netherlands
        • Site NL31003
      • Nijmegen, Netherlands
        • Site NL31009
      • Tilburg, Netherlands
        • Site NL31001
  • Portugal
      • Lisboa, Portugal
        • Site PT35105
      • Lisbon, Portugal
        • Site PT35102
      • Porto, Portugal
        • Site PT35106
  • Russian Federation
      • Ivanovo, Russian Federation
        • Site RU70002
      • Obninsk, Russian Federation
        • Site RU70009
      • Omsk, Russian Federation
        • Site RU70005
      • Vologda, Russian Federation
        • Site RU70015
  • Spain
      • Badajoz, Spain
        • Site ES34010
      • Badalona, Spain
        • Site ES34002
      • Barcelona, Spain
        • Site ES34001
      • Barcelona, Spain
        • Site ES34012
      • Barcelona, Spain
        • Site ES34023
      • Córdoba, Spain
        • Site ES34014
      • Madrid, Spain
        • Site ES34003
      • Madrid, Spain
        • Site ES34013
      • Madrid, Spain
        • Site ES34015
      • Madrid, Spain
        • Site ES34017
      • Manresa, Spain
        • Site ES34011
      • Pamplona, Spain
        • Site ES34019
      • Seville, Spain
        • Site ES34005
      • Valencia, Spain
        • Site ES34007
      • Valencia, Spain
        • Site ES34008
  • Switzerland
      • Bern, Switzerland
        • Site CH41002
      • Chur, Switzerland
        • Site CH41001
  • Taiwan
      • Kaohsiung, Taiwan
        • Site TW88602
      • Kaohsiung, Taiwan
        • Site TW88605
      • Taichung, Taiwan
        • Site TW88606
      • Tainan, Taiwan
        • Site TW88601
      • Taipei, Taiwan
        • Site TW88604
      • Taoyuan, Taiwan
        • Site TW88607
  • United Kingdom
      • London, United Kingdom
        • Site GB44005
      • London, United Kingdom
        • Site GB44006
      • Sheffield, United Kingdom
        • Site GB44002
      • Southampton, United Kingdom
        • Site GB44011
      • Sutton, United Kingdom
        • Site GB44013
      • Wirral, United Kingdom
        • Site GB44004
  • United States
    • California
      • Orange, California, United States, 92868
        • UCI Chao Family Comprehensive Cancer Center
      • Sacramento, California, United States, 95817
        • University of California
      • Whittier, California, United States, 90606
        • Innovative Clinical Research
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Hospital at Yale-New Haven
    • Florida
      • Miami, Florida, United States, 33136
        • Sylvester Comprehensive Cancer Center
      • Orlando, Florida, United States, 32804
        • Florida Hospital
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Norton Cancer Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Nebraska Cancer Specialists
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Lake Success, New York, United States, 11042
        • Long Island Jewish Medical Center
      • New York, New York, United States, 10065
        • Sidney Kimmel Center for Prostate and Urologic Cancers
      • White Plains, New York, United States, 10601
        • White Plains Hospital Center for Cancer Care - Oncology Site
    • Ohio
      • Toledo, Ohio, United States, 43623
        • Toledo Clinic Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Med Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Lifespan Rhode Island Hospital
    • South Carolina
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Hospital
    • Texas
      • Tyler, Texas, United States, 75701
        • HOPE Cancer Center of East Texas
    • Washington
      • Seattle, Washington, United States, 98101
        • Benaroya Research Institute at Virginia Mason
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Enfortumab Vedotin 1.25 mg/kg
Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
Drug: Enfortumab Vedotin
Intravenous infusion
Other Names:
  • ASG-22CE
  • ASG-22ME
Active Comparator: Arm B: Chemotherapy
Participants received either 75 milligrams per square meter (mg/m^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
Drug: Docetaxel
Intravenous infusion
Drug: Vinflunine
Intravenous infusion
Drug: Paclitaxel
Intravenous infusion
Experimental: Cross-over Extension (COE)
Eligible participants from chemotherapy arm who met the criteria for COE will receive 1.25 mg/kg of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle until discontinuation criteria is met.
Drug: Enfortumab Vedotin
Intravenous infusion
Other Names:
  • ASG-22CE
  • ASG-22ME

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
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.
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
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.
From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
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.
From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
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.
Baseline and week 12
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).
Baseline and week 12
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.
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)
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astellas Pharma Global Development, Inc.

Collaborators

Seagen Inc.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2018

Primary Completion (Actual)

July 15, 2020

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

March 16, 2018

First Submitted That Met QC Criteria

March 16, 2018

First Posted (Actual)

March 22, 2018

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7465-CL-0301
  • 2017-003344-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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