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

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ClinicalTrials.gov Identifier: NCT03219333
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : November 8, 2018
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, 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

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
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 : September 20, 2017
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : May 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) by an independent review facility (IRF) [ Time Frame: Up to 3 years ]
    The proportion of patients with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)


Secondary Outcome Measures :
  1. Duration of response (DOR) by an IRF [ Time Frame: Up to 7.5 years ]
    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

  2. Disease control rate at 16 weeks (DCR16) by an IRF [ Time Frame: 16 weeks ]
    Proportion of patients with CR, PR, or stable disease (SD) at Week 16 visit

  3. Progression free survival (PFS) by an IRF [ Time Frame: Up to 7.5 years ]
    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

  4. ORR by investigator assessment [ Time Frame: Up to 7.5 years ]
    Confirmed CR and PR per RECIST 1.1

  5. DOR by investigator assessment [ Time Frame: Up to 7.5 years ]
    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

  6. DCR16 by investigator assessment [ Time Frame: 16 weeks ]
    Proportion of patients with CR, PR, or SD at Week 16 visit

  7. Progression free survival (PFS) by investigator assessment [ Time Frame: Up to 7.5 years ]
    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

  8. Overall survival (OS) [ Time Frame: Up to 7.5 years ]
    The time from start of study treatment to date of death due to any cause

  9. Type, incidence, severity, seriousness, and relatedness of adverse events (AEs) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Descriptive statistics will be used to summarize results

  10. Laboratory abnormalities [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Descriptive statistics will be used to summarize results

  11. Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Cmax will be derived from the PK blood samples collected

  12. PK parameter for enfortumab vedotin: Trough concentration (Ctrough) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Ctrough will be derived from the PK blood samples collected

  13. PK parameter for monomethyl auristatin E (MMAE): Cmax [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Cmax will be derived from the PK blood samples collected

  14. PK parameter for MMAE: Ctrough [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Ctrough will be derived from the PK blood samples collected

  15. Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Blood samples for ATA analysis will be collected



Information from the National Library of Medicine

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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 0 or 1.

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


Contacts
Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

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Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Seattle Genetics, Inc.
Investigators
Study Director: Juan Pinelli, PA-C, MMScMD Seattle Genetics, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03219333     History of Changes
Other Study ID Numbers: SGN22E-001
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, 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:
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