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A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201)

Primary Purpose

Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Enfortumab vedotin
Sponsored by
Astellas Pharma Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Transitional Cell focused on measuring Enfortumab vedotin, Metastatic Urothelial Cancer, ASG-22CE, Locally Advanced Urothelial Cancer, Antibody-Drug Conjugate, Nectin-4, Platinum-naïve, Cisplatin-ineligible, Antineoplastic Agents, Drug Therapy, ASG-22ME

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
  • Metastatic disease or locally advanced disease that is not resectable.
  • Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
  • Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
  • Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
  • Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
  • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2.
  • Anticipated life expectancy of ≥3 months as assessed by the investigator.

Exclusion Criteria:

  • Ongoing sensory or motor neuropathy Grade ≥2.
  • Active central nervous system (CNS) metastases.
  • Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
  • Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
  • Uncontrolled tumor-related pain or impending spinal cord compression.

Sites / Locations

  • Alaska Urological Institute
  • Arizona Oncology Associates, PC - HAL
  • Mayo Clinic Arizona
  • Arizona Oncology Associates, PC - HOPE
  • Keck Medical Center / University of Southern California
  • Keck Medical Center / Newport Beach
  • Kaiser Permanente Oakland
  • Chao Family Comprehensive Cancer Center University of California Irvine
  • University of California Irvine - Newport
  • Kaiser Permanente Roseville
  • University of California Davis
  • Kaiser Permanente Sacramento
  • Kaiser Permanente San Francisco
  • Kaiser Permanente San Jose
  • Kaiser Permanente San Leandro
  • Kaiser Permanente Santa Clara
  • Kaiser Permanente South San Francisco
  • Kaiser Permanente Medical Center Northern California
  • Kaiser Permanente Walnut Creek
  • Rocky Mountain Cancer Centers - Aurora
  • Yale Cancer Center
  • Ocala Oncology Center
  • H. Lee Moffitt Cancer Center & Research Institute
  • Augusta University
  • University of Chicago Medical Center
  • Norton Cancer Institute, St. Matthews Campus
  • Johns Hopkins Medical Center
  • Maryland Oncology Hematology, P.A.
  • Massachusetts General Hospital
  • Dana Farber Cancer Institute
  • Karmanos Cancer Institute / Wayne State University
  • Washington University in St Louis
  • Comprehensive Cancer Centers of Nevada
  • New York Oncology Hematology, P.C.
  • New York University (NYU) Cancer Institute
  • Mount Sinai Medical Center
  • Columbia University Medical Center
  • Memorial Sloan Kettering Cancer Center
  • James P. Wilmot Cancer Center / University of Rochester Medical Center
  • Duke University Medical Center
  • Cleveland Clinic
  • James Cancer Hospital / Ohio State University
  • Northwest Cancer Specialists, P.C.
  • Thomas Jefferson University
  • University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
  • Prisma Health
  • Vanderbilt University Medical Center
  • Texas Oncology - Austin Central
  • Texas Oncology - Baylor Sammons Cancer Center
  • Houston Methodist Cancer Center
  • University of Virginia
  • Virginia Cancer Specialists, PC
  • Virginia Oncology Associates
  • Seattle Cancer Care Alliance / University of Washington
  • Site FR33001
  • Site DE49004
  • Site DE49001
  • Site IT39001
  • Site IT39003
  • Site JP81001
  • Site JP81004
  • Site JP81002
  • Site JP81008
  • Site JP81006
  • Site JP81009
  • Site JP81005
  • Site JP81011
  • Site JP81012
  • Site JP81003
  • Site JP81007
  • Site JP81010
  • Site KR82005
  • Site KR82003
  • Site KR82001
  • Site KR82002
  • Site KR82004
  • Site NL31001
  • Site ES34002
  • Site ES34005
  • Site ES34003
  • Site ES34004

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Enfortumab vedotin

Arm Description

Enfortumab vedotin on days 1, 8 and 15 every 28 days

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Secondary Outcome Measures

Duration of Objective Response (DOR) Per BICR
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression. DOR was analyzed using Kaplan-Meier methodology.
Progression-Free Survival (PFS) Per BICR
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint.
ORR Per Investigator Assessment
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR and PR are defined in the ORR per BICR endpoint.
DOR Per Investigator Assessment
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD is defined in the DOR per BICR endpoint.
PFS Per Investigator Assessment
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint.
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.
Incidence of Antitherapeutic Antibody (ATA)
Participants who were tested positive for ATA at any time post-baseline were considered to be transiently positive or persistently positive if >=2 consecutive samples were confirmed as positive.
Disease Control Rate at 16 Weeks (DCR16) Per BICR
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
DCR16 Per Investigator Assessment
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD is defined in DCR16 per BICR endpoint.
Overall Survival (OS) at Time of Primary Analysis
OS is defined as the time from first dose of enfortumab vedotin to death from any cause. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion.
Number of Participants With Adverse Events (AEs) at Time of Primary Analysis
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion.
Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)
AUC was derived from the PK blood samples collected.
PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
PK Parameter for Free MMAE: Tmax (Plasma)
Tmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
PK Parameter for Free MMAE: AUC (Plasma)
AUC was derived from the PK blood samples collected.
PK Parameter for Total Antibody (TAb): Cmax (Serum)
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
PK Parameter for TAb: Tmax (Serum)
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
PK Parameter for TAb: AUC (Serum)
AUC was derived from the PK blood samples collected.
Overall Survival (OS)
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment.

Full Information

First Posted
July 13, 2017
Last Updated
September 27, 2023
Sponsor
Astellas Pharma Inc
Collaborators
Seagen Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03219333
Brief Title
A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Acronym
EV-201
Official Title
A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
October 8, 2017 (Actual)
Primary Completion Date
October 27, 2020 (Actual)
Study Completion Date
July 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc
Collaborators
Seagen Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer. This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect. Patients who sign up for this trial must also fall into one of these categories: Patients have already received treatment with platinum-containing chemotherapy Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.
Detailed Description
Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan. This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously to patients with locally advanced or metastatic urothelial cancer who previously received a CPI and either previously received platinum-containing chemotherapy (Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of completion will be considered platinum-naïve. Approximately 100 patients are expected to be enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of enfortumab vedotin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms, Renal Pelvis Neoplasms, Urothelial Cancer, Ureteral Neoplasms, Urethral Neoplasms
Keywords
Enfortumab vedotin, Metastatic Urothelial Cancer, ASG-22CE, Locally Advanced Urothelial Cancer, Antibody-Drug Conjugate, Nectin-4, Platinum-naïve, Cisplatin-ineligible, Antineoplastic Agents, Drug Therapy, ASG-22ME

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
single-arm, open-label, multi-cohort, multicenter study
Masking
None (Open Label)
Allocation
N/A
Enrollment
219 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Enfortumab vedotin
Arm Type
Experimental
Arm Description
Enfortumab vedotin on days 1, 8 and 15 every 28 days
Intervention Type
Drug
Intervention Name(s)
Enfortumab vedotin
Other Intervention Name(s)
ASG-22CE, ASG-22ME
Intervention Description
Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
Description
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Secondary Outcome Measure Information:
Title
Duration of Objective Response (DOR) Per BICR
Description
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression. DOR was analyzed using Kaplan-Meier methodology.
Time Frame
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Title
Progression-Free Survival (PFS) Per BICR
Description
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint.
Time Frame
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Title
ORR Per Investigator Assessment
Description
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR and PR are defined in the ORR per BICR endpoint.
Time Frame
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Title
DOR Per Investigator Assessment
Description
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD is defined in the DOR per BICR endpoint.
Time Frame
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Title
PFS Per Investigator Assessment
Description
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint.
Time Frame
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Title
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
Description
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.
Time Frame
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]).
Title
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)
Description
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.
Time Frame
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]).
Title
Incidence of Antitherapeutic Antibody (ATA)
Description
Participants who were tested positive for ATA at any time post-baseline were considered to be transiently positive or persistently positive if >=2 consecutive samples were confirmed as positive.
Time Frame
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]).
Title
Disease Control Rate at 16 Weeks (DCR16) Per BICR
Description
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame
Up to Week 16. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2.
Title
DCR16 Per Investigator Assessment
Description
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD is defined in DCR16 per BICR endpoint.
Time Frame
Up to Week 16. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2.
Title
Overall Survival (OS) at Time of Primary Analysis
Description
OS is defined as the time from first dose of enfortumab vedotin to death from any cause. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion.
Time Frame
Up to data cut-off date of 08 Sept 2020 (Cohort 1 median follow-up time: 28.4 months [range 0.49, 32.62]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]).
Title
Number of Participants With Adverse Events (AEs) at Time of Primary Analysis
Description
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion.
Time Frame
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]).
Title
Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)
Description
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Time Frame
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22.
Title
PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)
Description
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Time Frame
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22.
Title
PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)
Description
AUC was derived from the PK blood samples collected.
Time Frame
Up to data cut-off date of 08 Sept 2020. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose).
Title
PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)
Description
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Time Frame
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22.
Title
PK Parameter for Free MMAE: Tmax (Plasma)
Description
Tmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Time Frame
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22.
Title
PK Parameter for Free MMAE: AUC (Plasma)
Description
AUC was derived from the PK blood samples collected.
Time Frame
Up to data cut-off date of 08 Sept 2020. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose).
Title
PK Parameter for Total Antibody (TAb): Cmax (Serum)
Description
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Time Frame
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22.
Title
PK Parameter for TAb: Tmax (Serum)
Description
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Time Frame
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22.
Title
PK Parameter for TAb: AUC (Serum)
Description
AUC was derived from the PK blood samples collected.
Time Frame
Up to data cut-off date of 08 Sept 2020. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose).
Title
Overall Survival (OS)
Time Frame
Updated Time Frame description will be provided at study completion.
Title
Number of Participants With Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment.
Time Frame
Updated Time Frame description will be provided at study completion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed). Metastatic disease or locally advanced disease that is not resectable. Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible. Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2). Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy. Tumor tissue samples must be available for submission to the sponsor prior to study treatment. Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1). An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2. Anticipated life expectancy of ≥3 months as assessed by the investigator. Exclusion Criteria: Ongoing sensory or motor neuropathy Grade ≥2. Active central nervous system (CNS) metastases. Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis. Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs). Uncontrolled tumor-related pain or impending spinal cord compression.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janet Trowbridge, MD, PhD
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Alaska Urological Institute
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99503
Country
United States
Facility Name
Arizona Oncology Associates, PC - HAL
City
Goodyear
State/Province
Arizona
ZIP/Postal Code
85395
Country
United States
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Arizona Oncology Associates, PC - HOPE
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
Facility Name
Keck Medical Center / University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Keck Medical Center / Newport Beach
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Kaiser Permanente Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Chao Family Comprehensive Cancer Center University of California Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California Irvine - Newport
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Kaiser Permanente Roseville
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Kaiser Permanente Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
Kaiser Permanente San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Kaiser Permanente San Jose
City
San Jose
State/Province
California
ZIP/Postal Code
95119
Country
United States
Facility Name
Kaiser Permanente San Leandro
City
San Leandro
State/Province
California
ZIP/Postal Code
94577
Country
United States
Facility Name
Kaiser Permanente Santa Clara
City
Santa Clara
State/Province
California
ZIP/Postal Code
95051
Country
United States
Facility Name
Kaiser Permanente South San Francisco
City
South San Francisco
State/Province
California
ZIP/Postal Code
94080
Country
United States
Facility Name
Kaiser Permanente Medical Center Northern California
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
Kaiser Permanente Walnut Creek
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94596
Country
United States
Facility Name
Rocky Mountain Cancer Centers - Aurora
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Ocala Oncology Center
City
Ocala
State/Province
Florida
ZIP/Postal Code
34474
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Norton Cancer Institute, St. Matthews Campus
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Johns Hopkins Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Maryland Oncology Hematology, P.A.
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute / Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Washington University in St Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
New York Oncology Hematology, P.C.
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
New York University (NYU) Cancer Institute
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
James P. Wilmot Cancer Center / University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
James Cancer Hospital / Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Tigard
State/Province
Oregon
ZIP/Postal Code
97223
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Prisma Health
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37204
Country
United States
Facility Name
Texas Oncology - Austin Central
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
Texas Oncology - Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Houston Methodist Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Virginia Cancer Specialists, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Seattle Cancer Care Alliance / University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
Facility Name
Site FR33001
City
Villejuif-Cedex-France
Country
France
Facility Name
Site DE49004
City
Muenster
Country
Germany
Facility Name
Site DE49001
City
Tübingen
Country
Germany
Facility Name
Site IT39001
City
Milano
Country
Italy
Facility Name
Site IT39003
City
Terni
Country
Italy
Facility Name
Site JP81001
City
Hirosaki
State/Province
Aomori
Country
Japan
Facility Name
Site JP81004
City
Tsukuba
State/Province
Ibaraki
Country
Japan
Facility Name
Site JP81002
City
Morioka
State/Province
Iwate
Country
Japan
Facility Name
Site JP81008
City
Osakasayama
State/Province
Osaka
Country
Japan
Facility Name
Site JP81006
City
Shinjuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Site JP81009
City
Ube
State/Province
Yamaguchi
Country
Japan
Facility Name
Site JP81005
City
Chiba
Country
Japan
Facility Name
Site JP81011
City
Fukuoka
Country
Japan
Facility Name
Site JP81012
City
Fukuoka
Country
Japan
Facility Name
Site JP81003
City
Nigata
Country
Japan
Facility Name
Site JP81007
City
Osaka
Country
Japan
Facility Name
Site JP81010
City
Tokushima
Country
Japan
Facility Name
Site KR82005
City
Daejeon
Country
Korea, Republic of
Facility Name
Site KR82003
City
Seongnam-si
Country
Korea, Republic of
Facility Name
Site KR82001
City
Seoul
Country
Korea, Republic of
Facility Name
Site KR82002
City
Seoul
Country
Korea, Republic of
Facility Name
Site KR82004
City
Seoul
Country
Korea, Republic of
Facility Name
Site NL31001
City
Amsterdam
Country
Netherlands
Facility Name
Site ES34002
City
Barcelona
Country
Spain
Facility Name
Site ES34005
City
Barcelona
Country
Spain
Facility Name
Site ES34003
City
Santander
Country
Spain
Facility Name
Site ES34004
City
Sevilla
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35168844
Citation
McGregor B, O'Donnell PH, Balar A, Petrylak D, Rosenberg J, Yu EY, Quinn DI, Heath EI, Campbell M, Hepp Z, McKay C, Steinberg J, Regnault A, Mazerolle F, Galsky MD. Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. Eur Urol. 2022 May;81(5):515-522. doi: 10.1016/j.eururo.2022.01.032. Epub 2022 Feb 12.
Results Reference
derived
PubMed Identifier
33991512
Citation
Yu EY, Petrylak DP, O'Donnell PH, Lee JL, van der Heijden MS, Loriot Y, Stein MN, Necchi A, Kojima T, Harrison MR, Hoon Park S, Quinn DI, Heath EI, Rosenberg JE, Steinberg J, Liang SY, Trowbridge J, Campbell M, McGregor B, Balar AV. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):872-882. doi: 10.1016/S1470-2045(21)00094-2. Epub 2021 May 12. Erratum In: Lancet Oncol. 2021 Jun;22(6):e239.
Results Reference
derived
PubMed Identifier
31356140
Citation
Rosenberg JE, O'Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, Galsky MD, Hahn NM, Gartner EM, Pinelli JM, Liang SY, Melhem-Bertrandt A, Petrylak DP. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019 Oct 10;37(29):2592-2600. doi: 10.1200/JCO.19.01140. Epub 2019 Jul 29.
Results Reference
derived

Learn more about this trial

A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

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