A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)

This study will test a drug called enfortumab vedotin in participants with a type of bladder cancer called non-muscle invasive bladder cancer (NMIBC).

This study will also evaluate what the side effects are and if the drug works to treat NMIBC. A side effect is anything a drug does to your body besides treating your disease.

In this study enfortumab vedotin will be put into the bladder using a catheter. A catheter is a thin tube that can be put into your bladder.

Study Overview

• Status: Terminated
• Conditions: Carcinoma in Situ; Urinary Bladder Neoplasms; Non-muscle Invasive Bladder Cancer; Carcinoma Transitional Cell; NMIBC
• Intervention / Treatment: Drug: Enfortumab vedotin

Detailed Description

The study will be comprised of 2 parts. The first part (dose escalation) will find the highest dose of enfortumab vedotin that does not cause unacceptable side effects in participants. The second part (dose expansion) will use the dose found in the first part to test how well the drug works.

All participants will receive enfortumab vedotin. Treatment on the study will occur during the induction and maintenance phases, and participants will enter a follow-up period after completion of the maintenance phase.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • Site CA11001
• France
  • Lyon, France, 69003
    • Site FR33002
  • Paris, France, 75013
    • Site FR33001
  • Rennes, France, 35000
    • Site FR33003
• Germany
  • Göttingen, Germany, 37075
    • Site DE49001
  • Tübingen, Germany, 72076
    • Site DE49002
• Spain
  • Barcelona, Spain, 08035
    • Site ES34004
  • Barcelona, Spain, 08036
    • Site ES34003
  • Barcelona, Spain, 08025
    • Site ES34001
  • Madrid, Spain, 28041
    • Site ES34002
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Site UK44002
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Department of Medicine - Hematology & Oncology
    • Orange, California, United States, 92868
      • University of California, Irvine
    • San Francisco, California, United States, 94134
      • University of California at San Francisco
    • Stanford, California, United States, 94305
      • Stanford Health Care
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University-Feinberg School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • Markey Cancer Center / University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medical Center
  • New York
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43221
      • James Cancer Hospital / Ohio State University
  • Oregon
    • Portland, Oregon, United States, 98682
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Oncology and Hematology
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio
  • Washington
    • Seattle, Washington, United States, 98195
      • Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
• Predominant histologic component (>50 percent) must be urothelial (transitional cell) carcinoma

• Participants must have high-risk Bacillus Calmette-Guerin (BCG) - unresponsive disease, defined as (where adequate BCG therapy is defined as one of the following: 5 of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second induction course):

  • Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
  • Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, or
  • T1 high-grade disease at the first evaluation following an induction BCG course (at least 5 or 6 doses)
• Participant must be ineligible for or refusing a radical cystectomy
• All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to enrollment.
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.

Exclusion Criteria:

• Current or prior history of muscle-invasive urothelial carcinoma or metastatic disease.
• Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months prior to study treatment
• Concomitant upper tract urothelial carcinoma as noted on CT or MRI urogram performed within 3 months prior to study treatment
• Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months prior to study treatment
• Participants with tumor-related hydronephrosis
• Participant has received other systemic anticancer therapy including chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational agent within 4 weeks or intravesical therapy within 6 weeks of first dose of study treatment
• Participant has had any prior radiation to the bladder for urothelial cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enfortumab vedotin: Dose escalation cohort; During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.	Drug: Enfortumab vedotin; Given into the bladder (intravesically); Other Names: PADCEV, ASG-22CE, ASG-22ME
Experimental: Enfortumab vedotin: Dose expansion cohort; During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.	Drug: Enfortumab vedotin; Given into the bladder (intravesically); Other Names: PADCEV, ASG-22CE, ASG-22ME

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)	An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Approximately 1 year
Incidence of laboratory abnormalities	To be summarized using descriptive statistics.	Approximately 1 year
Incidence of dose limiting toxicities (DLTs)	To be summarized using descriptive statistics.	Approximately 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of enfortumab vedotin: Area under the concentration-time curve (AUC)	AUC will be recorded from the PK blood samples collected.	Approximately 1 year
PK of enfortumab vedotin: Maximum concentration (Cmax)	Cmax will be recorded from the PK blood samples collected.	Approximately 1 year
PK of enfortumab vedotin: Time to maximum concentration concentration (tmax)	Tmax will be recorded from the PK blood samples collected.	Approximately 1 year
PK of enfortumab vedotin: Apparent terminal half-life (t1/2)	T1/2 will be recorded from the PK blood samples collected.	Approximately 1 year
PK of enfortumab vedotin: Trough concentration (Ctrough)	Ctrough will be recorded from the PK blood samples collected.	Approximately 1 year
Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin	Blood samples for ATA analysis will be collected.	Approximately 1 year
Complete response (CR) rate	CR rate is defined as the proportion of subjects achieving CR.	Up to 24 months
Duration of CR	The time from first documented CR to the first evidence of recurrence, progression, or death due to any cause.	Up to 5 years
Rate of cystectomy	The proportion of subjects who subsequently undergo cystectomy.	Up to 5 years
Progression-free survival	The time from start of study treatment to the first evidence of progression or death due to any cause.	Up to 5 years
Cystectomy-free survival	The time from start of study treatment to cystectomy or death due to any cause.	Up to 5 years

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Seagen, a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2021
• Primary Completion (Actual): September 22, 2025
• Study Completion (Actual): September 22, 2025

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bladder Cancer; Urothelial Cancer; Enfortumab vedotin; PADCEV
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Carcinoma in Situ; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; enfortumab vedotin
• Other Study ID Numbers: SGN22E-004; EV-104 (Other Identifier: Seagen, Inc.); C5701004 (Other Identifier: Pfizer); 2023-503388-40-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No