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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03219333
Recruitment Status : Active, not recruiting
First Posted : July 17, 2017
Results First Posted : December 17, 2021
Last Update Posted : June 15, 2022
Sponsor:
Collaborator:
Seagen Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Transitional Cell Urinary Bladder Neoplasms Urologic Neoplasms Renal Pelvis Neoplasms Urothelial Cancer Ureteral Neoplasms Urethral Neoplasms Drug: Enfortumab vedotin Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 219 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: single-arm, open-label, multi-cohort, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 8, 2017
Actual Primary Completion Date : October 27, 2020
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Enfortumab vedotin
Enfortumab vedotin on days 1, 8 and 15 every 28 days
Drug: Enfortumab vedotin
Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
Other Names:
  • ASG-22CE
  • ASG-22ME




Primary Outcome Measures :
  1. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) [ 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]). ]
    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 :
  1. Duration of Objective Response (DOR) Per BICR [ 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]). ]
    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.

  2. Progression-Free Survival (PFS) Per BICR [ 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]). ]
    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.

  3. ORR Per Investigator Assessment [ 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]). ]
    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.

  4. DOR Per Investigator Assessment [ 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]). ]
    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.

  5. PFS Per Investigator Assessment [ 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]). ]
    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.

  6. Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) [ 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]). ]
    A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.

  7. Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) [ 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]). ]
    A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.

  8. Incidence of Antitherapeutic Antibody (ATA) [ 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]). ]
    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. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2. ]
    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.

  10. DCR16 Per Investigator Assessment [ Time Frame: Up to Week 16. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2. ]
    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.

  11. Overall Survival (OS) at Time of Primary Analysis [ 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]). ]
    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.

  12. Number of Participants With Adverse Events (AEs) at Time of Primary Analysis [ 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]). ]
    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.

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

  15. PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) [ 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). ]
    AUC was derived from the PK blood samples collected.

  16. PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) [ 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. ]
    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: 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. ]
    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: 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). ]
    AUC was derived from the PK blood samples collected.

  19. PK Parameter for Total Antibody (TAb): Cmax (Serum) [ 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. ]
    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: 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. ]
    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: 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). ]
    AUC was derived from the PK blood samples collected.

  22. Overall Survival (OS) [ Time Frame: Updated Time Frame description will be provided at study completion. ]
  23. Number of Participants With Adverse Events (AEs) [ Time Frame: Updated Time Frame description will be provided at study completion. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219333


Locations
Show Show 81 study locations
Sponsors and Collaborators
Astellas Pharma Inc
Seagen Inc.
Investigators
Layout table for investigator information
Study Director: Janet Trowbridge, MD, PhD Seagen Inc.
  Study Documents (Full-Text)

Documents provided by Astellas Pharma Inc:
Study Protocol  [PDF] December 5, 2019
Statistical Analysis Plan  [PDF] September 17, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT03219333    
Other Study ID Numbers: SGN22E-001
First Posted: July 17, 2017    Key Record Dates
Results First Posted: December 17, 2021
Last Update Posted: June 15, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc:
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
Additional relevant MeSH terms:
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Neoplasms
Urinary Bladder Neoplasms
Urologic Neoplasms
Carcinoma, Transitional Cell
Ureteral Neoplasms
Urethral Neoplasms
Pelvic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Ureteral Diseases
Urethral Diseases