Clinical Trial - NCT03219333

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

Recruiting

Sponsor: Astellas Pharma Global Development, Inc.

Collaborators: Seattle Genetics, Inc.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03219333

Protocol Info

Short Description: A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201)
Long Description: 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
MGH Status: Open
Sponsor: Seattle Genetics
Disease Program: GU

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




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.
Condition Title Intervention Phase
Carcinoma, Transitional Cell Urinary Bladder Neoplasms Urologic Neoplasms Renal Pelvis Neoplasms Urothelial Cancer Ureteral Neoplasms Urethral Neoplasms Enfortumab vedotin Phase 2
Study Type Interventional
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

Primary Outcome Measures

Objective response rate (ORR) by an independent review facility (IRF) [Time Frame: Up to 3 years] [Designated as safety issue: ]


Secondary Outcome Measures

Duration of response (DOR) by an IRF [Time Frame: Up to 7.5 years] [Designated as safety issue: ]

Disease control rate at 16 weeks (DCR16) by an IRF [Time Frame: 16 weeks] [Designated as safety issue: ]

Progression free survival (PFS) by an IRF [Time Frame: Up to 7.5 years] [Designated as safety issue: ]

ORR by investigator assessment [Time Frame: Up to 7.5 years] [Designated as safety issue: ]

DOR by investigator assessment [Time Frame: Up to 7.5 years] [Designated as safety issue: ]

DCR16 by investigator assessment [Time Frame: 16 weeks] [Designated as safety issue: ]

Progression free survival (PFS) by investigator assessment [Time Frame: Up to 7.5 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: Up to 7.5 years] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Estimated Enrollment: 200
Study Start Date: October 2017
Estimated Study Completion Date: May 2025
Estimated Primary Completion Date: November 2020
Arms Assigned Interventions

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

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03219333

Locations

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

Sponsors and Collaborators

Astellas Pharma Global Development, Inc.

Seattle Genetics, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03219333
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

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:

Neoplasms

Urinary Bladder Neoplasms

Urologic Neoplasms

Carcinoma, Transitional Cell

Ureteral Neoplasms

Urethral Neoplasms

Pelvic Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019