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


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

Intervention:

  • Drug: Enfortumab 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03219333

Sponsor: Astellas Pharma Global Development, Inc.

Primary Outcome Measures:

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

Secondary Outcome Measures:

  • Measure: Duration of response (DOR) by an IRF
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: Disease control rate at 16 weeks (DCR16) by an IRF
  • Time Frame: 16 weeks
  • Safety Issue:
  • Measure: Progression free survival (PFS) by an IRF
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: ORR by investigator assessment
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: DOR by investigator assessment
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: DCR16 by investigator assessment
  • Time Frame: 16 weeks
  • Safety Issue:
  • Measure: Progression free survival (PFS) by investigator assessment
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: Incidence 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:
  • Measure: Incidence of 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:
  • 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:
  • 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:
  • 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:
  • 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:
  • Measure: PK parameter for Total Antibody (TAb): Cmax
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: PK parameter for Total Antibody (TAb): Ctrough
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • 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:

Estimated Enrollment: 200

Study Start Date: October 8, 2017

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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.

Contact:

  • Seattle Genetics Trial Information Support
  • 866-333-7436

Locations:

  • Alaska Urological Institute
  • Anchorage Alaska 99503 United States
  • Mayo Clinic Arizona
  • Scottsdale Arizona 85259 United States
  • Arizona Oncology Associates, PC - HOPE
  • Tucson Arizona 85710 United States
  • University of California Davis
  • Davis California 95616 United States
  • Keck Medical Center / University of Southern California
  • Los Angeles California 90033 United States
  • Keck Medical Center / Newport Beach
  • Newport Beach California 92663 United States
  • Kaiser Permanente Oakland
  • Oakland California 94611 United States
  • Chao Family Comprehensive Cancer Center University of California Irvine
  • Orange California 92868 United States
  • University of California Irvine - Newport
  • Orange California 92868 United States
  • Kaiser Permanente Roseville
  • Roseville California 95661 United States
  • Kaiser Permanente Sacramento
  • Sacramento California 95825 United States
  • Kaiser Permanente San Francisco
  • San Francisco California 94115 United States
  • Kaiser Permanente San Jose
  • San Jose California 95119 United States
  • Kaiser Permanente San Leandro
  • San Leandro California 94577 United States
  • Kaiser Permanente Santa Clara
  • Santa Clara California 95051 United States
  • Kaiser Permanente South San Francisco
  • South San Francisco California 94080 United States
  • Kaiser Permanente Medical Center Northern California
  • Vallejo California 94589 United States
  • Kaiser Permanente Walnut Creek
  • Walnut Creek California 94596 United States
  • Rocky Mountain Cancer Centers - Aurora
  • Aurora Colorado 80012 United States
  • Yale Cancer Center
  • New Haven Connecticut 06520 United States
  • Ocala Oncology Center
  • Ocala Florida 34471 United States
  • H. Lee Moffitt Cancer Center & Research Institute
  • Tampa Florida 33612 United States
  • Augusta University
  • Augusta Georgia 30912 United States
  • University of Chicago
  • Chicago Illinois 60637-1470 United States
  • Norton Cancer Institute
  • Louisville Kentucky 40202 United States
  • Johns Hopkins Medical Center
  • Baltimore Maryland 21231 United States
  • Maryland Oncology Hematology, P.A.
  • Silver Spring Maryland 20904 United States
  • Massachusetts General Hospital
  • Boston Massachusetts 02114 United States
  • Dana Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Karmanos Cancer Institute / Wayne State University
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • New York Oncology Hematology, P.C.
  • Albany New York 12206 United States
  • New York University (NYU) Cancer Institute
  • New York New York 10016 United States
  • Columbia University Medical Center
  • New York New York 10022 United States
  • Mount Sinai Medical Center
  • New York New York 10029 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10087-9049 United States
  • James P. Wilmot Cancer Center / University of Rochester Medical Center
  • Rochester New York 14642 United States
  • Duke University Medical Center
  • Durham North Carolina 27710 United States
  • Cleveland Clinic, The
  • Cleveland Ohio 44195 United States
  • James Cancer Hospital / Ohio State University
  • Columbus Ohio 43210 United States
  • Northwest Cancer Specialists, P.C.
  • Tualatin Oregon 97062 United States
  • Thomas Jefferson University
  • Philadelphia Pennsylvania 19107 United States
  • Hillman Cancer Center / University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Health System Cancer Institute
  • Greenville South Carolina 29615 United States
  • Vanderbilt University Medical Center
  • Nashville Tennessee 37204 United States
  • Texas Oncology - Austin Central
  • Austin Texas 78731 United States
  • Texas Oncology - Baylor Sammons Cancer Center
  • Dallas Texas 75246 United States
  • Houston Methodist Cancer Center
  • Houston Texas 77030 United States
  • University of Virginia
  • Charlottesville Virginia 22908 United States
  • Virginia Cancer Specialists, PC
  • Fairfax Virginia 22031 United States
  • Virginia Oncology Associates
  • Norfolk Virginia 23502 United States
  • Seattle Cancer Care Alliance / University of Washington
  • Seattle Washington 98109-1023 United States
  • Site FR33001
  • Villejuif-Cedex-France France
  • Site DE49004
  • Muenster Germany
  • Site DE49001
  • Tübingen Germany
  • Site IT39001
  • Milano Italy
  • Site IT39003
  • Terni Italy
  • Site JP81001
  • Hirosaki Aomori Japan
  • Site JP81004
  • Tsukuba Ibaraki Japan
  • Site JP81002
  • Morioka Iwate Japan
  • Site JP81008
  • Osakasayama Osaka Japan
  • Site JP81006
  • Shinjuku-ku Tokyo Japan
  • Site JP81009
  • Ube Yamaguchi Japan
  • Site JP81005
  • Chiba Japan
  • Site JP81011
  • Fukuoka Japan
  • Site JP81012
  • Fukuoka Japan
  • Site JP81003
  • Nigata Japan
  • Site JP81007
  • Osaka Japan
  • Site JP81010
  • Tokushima Japan
  • Site KR82005
  • Daejeon Korea, Republic of
  • Site KR82003
  • Seongnam-si Korea, Republic of
  • Site KR82001
  • Seoul Korea, Republic of
  • Site KR82002
  • Seoul Korea, Republic of
  • Site KR82004
  • Seoul Korea, Republic of
  • Site NL31001
  • Amsterdam Netherlands
  • Site ES34002
  • Barcelona Spain
  • Site ES34003
  • Santander Spain
  • Site ES34004
  • Sevilla Spain

View trial on ClinicalTrials.gov


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