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NCT Number: NCT03219333

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

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.

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Key information

Conditions

Carcinoma, Transitional Cell Carcinoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Renal Pelvis Neoplasms Ureteral Diseases Ureteral Neoplasms Urethral Diseases Urethral Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Urothelial Cancer

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Site FR33001, Villejuif-Cedex-France, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Enfortumab vedotin

Drug

Intravenous (IV) infusion on days 1, 8 and 15 every 28 days

Other names: ASG-22CE, ASG-22ME

Primary outcomes

  1. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)

    Time frame: 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)

    ORR was defined as 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 outcomes

  1. Duration of Objective Response (DOR) Per BICR

    Time frame: 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)

    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 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. 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.

  2. Progression-Free Survival (PFS) Per BICR

    Time frame: 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)

    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 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.

  3. ORR Per Investigator Assessment

    Time frame: 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)

    ORR was defined as the percentage of participants with confirmed CR or PR according to 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.

  4. DOR Per Investigator Assessment

    Time frame: 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)

    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. 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.

  5. PFS Per Investigator Assessment

    Time frame: 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)

    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 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.

  6. Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)

    Time frame: 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]

    A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.

  7. Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)

    Time frame: 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]

    A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. Abnormalities were graded based NCI CTCAE version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.

  8. Incidence of Antitherapeutic Antibody (ATA)

    Time frame: 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]

    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.

  9. Disease Control Rate at 16 Weeks (DCR16) Per BICR

    Time frame: Up to Week 16

    Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. 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. 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.

  10. DCR16 Per Investigator Assessment

    Time frame: Up to Week 16

    Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. 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. 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. 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.

  11. Overall Survival (OS): Primary Analysis

    Time frame: 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]

    OS is defined as the time from first dose of enfortumab vedotin to death from any cause.

  12. Number of Participants With Adverse Events (AEs): Primary Analysis

    Time frame: 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]

    AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator.

  13. Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)

    Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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

    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.

  14. PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)

    Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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

    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.

  15. PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)

    Time frame: 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)

    AUC was derived from the PK blood samples collected.

  16. PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)

    Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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

    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.

  17. PK Parameter for Free MMAE: Tmax (Plasma)

    Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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

    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.

  18. PK Parameter for Free MMAE: AUC (Plasma)

    Time frame: 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)

    AUC was derived from the PK blood samples collected.

  19. PK Parameter for Total Antibody (TAb): Cmax (Serum)

    Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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

    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.

  20. PK Parameter for TAb: Tmax (Serum)

    Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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

    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.

  21. PK Parameter for TAb: AUC (Serum)

    Time frame: 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)

    AUC was derived from the PK blood samples collected.

  22. Number of Participants With Adverse Events (AEs): Final Analysis

    Time frame: Cohort 1: median treatment duration time: 4.60 months (range 0.5, 43.0); Cohort 2: median treatment duration time: 5.98 months (range 0.3 to 25.8)

    AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator.

  23. Overall Survival (OS): Final Analysis

    Time frame: Cohort 1: median follow-up: 61.0 months (range 59.63, 62.36); Cohort 2: median follow-up time: 45.8 months (range 44.91 to 48.95)

    OS is defined as the time from first dose of enfortumab vedotin to death from any cause.

Sponsors and collaborators

Lead sponsor

Astellas Pharma Inc

Industry

Collaborators

  • Seagen Inc.

Registry information

Official study 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

Acronym: EV-201

Important dates

Study start
2017
Primary completion
2020
Study completion
2023
First posted
Jul 17, 2017
Registry last updated
Aug 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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