A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201)

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborator: Seattle Genetics, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Urologic Neoplasms; Renal Pelvis Neoplasms; Urothelial Cancer; Ureteral Neoplasms; Urethral Neoplasms	Drug: Enfortumab vedotin	Phase 2

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Intervention Model:	Single Group Assignment
Intervention Model Description:	single-arm, open-label, multi-cohort, multicenter study
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	October 8, 2017
Estimated Primary Completion Date :	November 2020
Estimated Study Completion Date :	May 2025

Arms and Interventions

Arm	Intervention/treatment
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; Other Names: ASG-22CE; ASG-22ME

Outcome Measures

Primary Outcome Measures :

1. Objective response rate (ORR) by an independent review facility (IRF) [ Time Frame: Up to 3 years ]
   The proportion of patients with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

Secondary Outcome Measures :

1. Duration of response (DOR) by an IRF [ Time Frame: Up to 7.5 years ]
   The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first
2. Disease control rate at 16 weeks (DCR16) by an IRF [ Time Frame: 16 weeks ]
   Proportion of patients with CR, PR, or stable disease (SD) at Week 16 visit
3. Progression free survival (PFS) by an IRF [ Time Frame: Up to 7.5 years ]
   The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
4. ORR by investigator assessment [ Time Frame: Up to 7.5 years ]
   Confirmed CR and PR per RECIST 1.1
5. DOR by investigator assessment [ Time Frame: Up to 7.5 years ]
   The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first
6. DCR16 by investigator assessment [ Time Frame: 16 weeks ]
   Proportion of patients with CR, PR, or SD at Week 16 visit
7. Progression free survival (PFS) by investigator assessment [ Time Frame: Up to 7.5 years ]
   The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
8. Overall survival (OS) [ Time Frame: Up to 7.5 years ]
   The time from start of study treatment to date of death due to any cause
9. 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 ]
   Descriptive statistics will be used to summarize results
10. 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 ]
    Descriptive statistics will be used to summarize results
11. 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 ]
    Cmax will be derived from the PK blood samples collected
12. 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 ]
    Ctrough will be derived from the PK blood samples collected
13. 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 ]
    Cmax will be derived from the PK blood samples collected
14. 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 ]
    Ctrough will be derived from the PK blood samples collected
15. 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 ]
    Cmax will be derived from the PK blood samples collected
16. 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 ]
    Ctrough will be derived from the PK blood samples collected
17. 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 ]
    Blood samples for ATA analysis will be collected

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Contacts

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Contact: Seattle Genetics Trial Information Support	866-333-7436	clinicaltrials@seagen.com

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Sponsors and Collaborators

Astellas Pharma Global Development, Inc.

Seattle Genetics, Inc.

Investigators

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Study Director:	Juan Pinelli, PA-C, MMSc	Seattle Genetics, Inc.

More Information

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Responsible Party:	Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier:	NCT03219333 History of Changes
Other Study ID Numbers:	SGN22E-001
First Posted:	July 17, 2017
Last Update Posted:	February 25, 2019
Last Verified:	February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, 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:

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Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Carcinoma, Transitional Cell; Ureteral Neoplasms; Urethral Neoplasms; Pelvic Neoplasms; Urogenital Neoplasms	Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ureteral Diseases; Urethral Diseases