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

NCT ID: NCT03219333

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-08
• Study Completion Date: 2023-07-28

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.

Detailed Description

Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Enfortumab vedotin

Enfortumab vedotin on days 1, 8 and 15 every 28 days

Group Type: EXPERIMENTAL

Enfortumab vedotin

Intervention Type: DRUG

Intravenous (IV) infusion on days 1, 8 and 15 every 28 days

Interventions

Enfortumab vedotin

Intravenous (IV) infusion on days 1, 8 and 15 every 28 days

Intervention Type: DRUG

Other Intervention Names

ASG-22CE; ASG-22ME

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janet Trowbridge, MD, PhD

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

Alaska Urological Institute

Anchorage, Alaska, United States

Arizona Oncology Associates, PC - HAL

Goodyear, Arizona, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

Keck Medical Center / University of Southern California

Los Angeles, California, United States

Keck Medical Center / Newport Beach

Newport Beach, California, United States

Kaiser Permanente Oakland

Oakland, California, United States

Chao Family Comprehensive Cancer Center University of California Irvine

Orange, California, United States

University of California Irvine - Newport

Orange, California, United States

Kaiser Permanente Roseville

Roseville, California, United States

University of California Davis

Sacramento, California, United States

Kaiser Permanente Sacramento

Sacramento, California, United States

Kaiser Permanente San Francisco

San Francisco, California, United States

Kaiser Permanente San Jose

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Kaiser Permanente Santa Clara

Santa Clara, California, United States

Kaiser Permanente South San Francisco

South San Francisco, California, United States

Kaiser Permanente Medical Center Northern California

Vallejo, California, United States

Kaiser Permanente Walnut Creek

Walnut Creek, California, United States

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Ocala Oncology Center

Ocala, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Augusta University

Augusta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, United States

Johns Hopkins Medical Center

Baltimore, Maryland, United States

Maryland Oncology Hematology, P.A.

Rockville, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, United States

Washington University in St Louis

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

New York University (NYU) Cancer Institute

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

James P. Wilmot Cancer Center / University of Rochester Medical Center

Rochester, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

James Cancer Hospital / Ohio State University

Columbus, Ohio, United States

Northwest Cancer Specialists, P.C.

Tigard, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Prisma Health

Greenville, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Oncology - Austin Central

Austin, Texas, United States

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, United States

Houston Methodist Cancer Center

Houston, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, United States

Site FR33001

Villejuif-Cedex-France, , France

Site DE49004

Münster, , Germany

Site DE49001

Tübingen, , Germany

Site IT39001

Milan, , Italy

Site IT39003

Terni, , Italy

Site JP81001

Hirosaki, Aomori, Japan

Site JP81004

Tsukuba, Ibaraki, Japan

Site JP81002

Morioka, Iwate, Japan

Site JP81003

Nigata, Niigata, Japan

Site JP81008

Sayama, 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 JP81007

Osaka, , Japan

Site JP81010

Tokushima, , Japan

Site NL31001

Amsterdam, , Netherlands

Site KR82005

Daejeon, , South Korea

Site KR82003

Seongnam-si, , South Korea

Site KR82001

Seoul, , South Korea

Site KR82002

Seoul, , South Korea

Site KR82004

Seoul, , South Korea

Site ES34002

Barcelona, , Spain

Site ES34005

Barcelona, , Spain

Site ES34003

Santander, , Spain

Site ES34004

Seville, , Spain

Countries

United States; France; Germany; Italy; Japan; Netherlands; South Korea; Spain

References

McGregor B, O'Donnell PH, Balar A, Petrylak D, Rosenberg J, Yu EY, Quinn DI, Heath EI, Campbell M, Hepp Z, McKay C, Steinberg J, Regnault A, Mazerolle F, Galsky MD. Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. Eur Urol. 2022 May;81(5):515-522. doi: 10.1016/j.eururo.2022.01.032. Epub 2022 Feb 12.

Reference Type: DERIVED

PMID: 35168844 (View on PubMed)

Yu EY, Petrylak DP, O'Donnell PH, Lee JL, van der Heijden MS, Loriot Y, Stein MN, Necchi A, Kojima T, Harrison MR, Hoon Park S, Quinn DI, Heath EI, Rosenberg JE, Steinberg J, Liang SY, Trowbridge J, Campbell M, McGregor B, Balar AV. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):872-882. doi: 10.1016/S1470-2045(21)00094-2. Epub 2021 May 12.

Reference Type: DERIVED

PMID: 33991512 (View on PubMed)

Rosenberg JE, O'Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, Galsky MD, Hahn NM, Gartner EM, Pinelli JM, Liang SY, Melhem-Bertrandt A, Petrylak DP. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019 Oct 10;37(29):2592-2600. doi: 10.1200/JCO.19.01140. Epub 2019 Jul 29.

Reference Type: DERIVED

PMID: 31356140 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SGN22E-001

Identifier Type: -

Identifier Source: org_study_id