A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Condition: Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Urologic Neoplasms; Renal Pelvis Neoplasms; Urothelial Cancer; Ureteral Neoplasms; Urethral Neoplasms
MeSH terms: Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Carcinoma, Transitional Cell; Ureteral Neoplasms; Urethral Neoplasms; Pelvic Neoplasms
Intervention: Enfortumab vedotin
Intervention description: Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: single-arm, open-label, multi-cohort, multicenter study
Masking: None (Open Label)
Enrollment: 219.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

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.