Clinical Trials /

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

NCT03219333

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: SGN22E-001
  • NCT ID: NCT03219333

Conditions

  • Carcinoma, Transitional Cell
  • Urinary Bladder Neoplasms
  • Urologic Neoplasms
  • Renal Pelvis Neoplasms
  • Urothelial Cancer
  • Ureteral Neoplasms
  • Urethral Neoplasms

Interventions

DrugSynonymsArms
Enfortumab vedotinASG-22CE, ASG-22MEEnfortumab vedotin

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Enfortumab vedotinExperimentalEnfortumab vedotin on days 1, 8 and 15 every 28 days
  • Enfortumab vedotin

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) by an independent review facility (IRF)
Time Frame:Up to 3 years
Safety Issue:
Description: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

Measure:Duration of response (DOR) by an IRF
Time Frame:Up to 7.5 years
Safety Issue:
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
Measure:Disease control rate at 16 weeks (DCR16) by an IRF
Time Frame:16 weeks
Safety Issue:
Description:Proportion of patients with CR, PR, or stable disease (SD) at Week 16 visit
Measure:Progression free survival (PFS) by an IRF
Time Frame:Up to 7.5 years
Safety Issue:
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
Measure:ORR by investigator assessment
Time Frame:Up to 7.5 years
Safety Issue:
Description:Confirmed CR and PR per RECIST 1.1
Measure:DOR by investigator assessment
Time Frame:Up to 7.5 years
Safety Issue:
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
Measure:DCR16 by investigator assessment
Time Frame:16 weeks
Safety Issue:
Description:Proportion of patients with CR, PR, or SD at Week 16 visit
Measure:Progression free survival (PFS) by investigator assessment
Time Frame:Up to 7.5 years
Safety Issue:
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
Measure:Overall survival (OS)
Time Frame:Up to 7.5 years
Safety Issue:
Description:The time from start of study treatment to date of death due to any cause
Measure: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
Safety Issue:
Description:Descriptive statistics will be used to summarize results
Measure:Laboratory abnormalities
Time Frame:Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
Safety Issue:
Description:Descriptive statistics will be used to summarize results
Measure: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
Safety Issue:
Description:Cmax will be derived from the PK blood samples collected
Measure: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
Safety Issue:
Description:Ctrough will be derived from the PK blood samples collected
Measure: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
Safety Issue:
Description:Cmax will be derived from the PK blood samples collected
Measure: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
Safety Issue:
Description:Ctrough will be derived from the PK blood samples collected
Measure: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
Safety Issue:
Description:Blood samples for ATA analysis will be collected

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial 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

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