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

NCT03219333 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SGN22E-001
• Study Type: interventional
• Target: 219
• Locations: 8 countries
• Sites: 81

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)

  ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)

Secondary Outcomes (23)

• Duration of Objective Response (DOR) Per BICR

  Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)

• Progression-Free Survival (PFS) Per BICR

  Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)

• ORR Per Investigator Assessment

  Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)

• DOR Per Investigator Assessment

  Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)

• PFS Per Investigator Assessment

  Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)

Study Arms (1)

Enfortumab vedotin

EXPERIMENTAL

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

Drug: Enfortumab vedotin

Interventions

Enfortumab vedotin DRUG

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

Also known as: ASG-22CE, ASG-22ME

Enfortumab vedotin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Seagen Inc.: collaborator

Study Sites (81)

Alaska Urological Institute

Anchorage, Alaska, 99503, United States

Location

Arizona Oncology Associates, PC - HAL

Goodyear, Arizona, 85395, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85710, United States

Location

Keck Medical Center / University of Southern California

Los Angeles, California, 90033, United States

Location

Keck Medical Center / Newport Beach

Newport Beach, California, 92663, United States

Location

Kaiser Permanente Oakland

Oakland, California, 94611, United States

Location

Chao Family Comprehensive Cancer Center University of California Irvine

Orange, California, 92868, United States

Location

University of California Irvine - Newport

Orange, California, 92868, United States

Location

Kaiser Permanente Roseville

Roseville, California, 95661, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

Kaiser Permanente Sacramento

Sacramento, California, 95825, United States

Location

Kaiser Permanente San Francisco

San Francisco, California, 94115, United States

Location

Kaiser Permanente San Jose

San Jose, California, 95119, United States

Location

Kaiser Permanente San Leandro

San Leandro, California, 94577, United States

Location

Kaiser Permanente Santa Clara

Santa Clara, California, 95051, United States

Location

Kaiser Permanente South San Francisco

South San Francisco, California, 94080, United States

Location

Kaiser Permanente Medical Center Northern California

Vallejo, California, 94589, United States

Location

Kaiser Permanente Walnut Creek

Walnut Creek, California, 94596, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Ocala Oncology Center

Ocala, Florida, 34474, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637-1470, United States

Location

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207, United States

Location

Johns Hopkins Medical Center

Baltimore, Maryland, 21231, United States

Location

Maryland Oncology Hematology, P.A.

Rockville, Maryland, 20850, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12208, United States

Location

New York University (NYU) Cancer Institute

New York, New York, 10016, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

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

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

James Cancer Hospital / Ohio State University

Columbus, Ohio, 43210, United States

Location

Northwest Cancer Specialists, P.C.

Tigard, Oregon, 97223, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

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

Pittsburgh, Pennsylvania, 15232, United States

Location

Prisma Health

Greenville, South Carolina, 29615, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37204, United States

Location

Texas Oncology - Austin Central

Austin, Texas, 78731, United States

Location

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Site FR33001

Villejuif-Cedex-France, France

Location

Site DE49004

Münster, Germany

Location

Site DE49001

Tübingen, Germany

Location

Site IT39001

Milan, Italy

Location

Site IT39003

Terni, Italy

Location

Site JP81001

Hirosaki, Aomori, Japan

Location

Site JP81004

Tsukuba, Ibaraki, Japan

Location

Site JP81002

Morioka, Iwate, Japan

Location

Site JP81003

Nigata, Niigata, Japan

Location

Site JP81008

Sayama, Osaka, Japan

Location

Site JP81006

Shinjuku-ku, Tokyo, Japan

Location

Site JP81009

Ube, Yamaguchi, Japan

Location

Site JP81005

Chiba, Japan

Location

Site JP81011

Fukuoka, Japan

Location

Site JP81012

Fukuoka, Japan

Location

Site JP81007

Osaka, Japan

Location

Site JP81010

Tokushima, Japan

Location

Site NL31001

Amsterdam, Netherlands

Location

Site KR82005

Daejeon, South Korea

Location

Site KR82003

Seongnam-si, South Korea

Location

Site KR82001

Seoul, South Korea

Location

Site KR82002

Seoul, South Korea

Location

Site KR82004

Seoul, South Korea

Location

Site ES34002

Barcelona, Spain

Location

Site ES34005

Barcelona, Spain

Location

Site ES34003

Santander, Spain

Location

Site ES34004

Seville, Spain

Location

Related Publications (3)

• 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.

  PMID: 35168844 DERIVED

• 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.

  PMID: 33991512 DERIVED

• 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.

  PMID: 31356140 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Urologic Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Interventions

enfortumab vedotin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Urethral Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seagen Inc.

medinfo@seagen.com

(855) 473-2436

Study Officials

• Janet Trowbridge, MD, PhD

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: single-arm, open-label, multi-cohort, multicenter study

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 17, 2017
• Study Start: October 8, 2017
• Primary Completion: October 27, 2020
• Study Completion: July 28, 2023
• Last Updated: August 27, 2024
• Results First Posted: December 17, 2021

Record last verified: 2024-08

Locations

FR (1); ES (4); NL (1); IT (2); KR (5); JP (12); DE (2); US (54)