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

Urinary Bladder Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05014139
• Other study ID #: SGN22E-004
• Secondary ID: EV-104
• Status: Recruiting
• Phase: Phase 1
• Start date: December 7, 2021
• Est. completion date: May 31, 2028

Study information

• Verified date: April 2024
• Source: Astellas Pharma Inc
• Contact: Seagen, Inc. Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: May 31, 2028
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma in Situ
• Carcinoma Transitional Cell
• Carcinoma, Transitional Cell
• NMIBC
• Non-muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Enfortumab vedotin
Given into the bladder (intravesically)

Locations

Country	Name	City	State
Canada	Site CA11001	Toronto	Ontario
France	Site FR33001	Paris
Spain	Site ES34001	Barcelona
Spain	Site ES34003	Barcelona
Spain	Site ES34002	Madrid
United Kingdom	Site UK44002	London
United States	Johns Hopkins Medical Center	Baltimore	Maryland
United States	James Cancer Hospital / Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	MD Anderson	Houston	Texas
United States	UCLA Department of Medicine - Hematology & Oncology	Los Angeles	California
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	University of California, Irvine	Orange	California
United States	Urology San Antonio	San Antonio	Texas
United States	University of California at San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Seagen Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of laboratory abnormalities	To be summarized using descriptive statistics.	Approximately 1 year
Primary	Incidence of dose limiting toxicities (DLTs)	To be summarized using descriptive statistics.	Approximately 7 weeks
Secondary	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
Secondary	PK of enfortumab vedotin: Maximum concentration (Cmax)	Cmax will be recorded from the PK blood samples collected.	Approximately 1 year
Secondary	PK of enfortumab vedotin: Time to maximum concentration concentration (tmax)	Tmax will be recorded from the PK blood samples collected.	Approximately 1 year
Secondary	PK of enfortumab vedotin: Apparent terminal half-life (t1/2)	T1/2 will be recorded from the PK blood samples collected.	Approximately 1 year
Secondary	PK of enfortumab vedotin: Trough concentration (Ctrough)	Ctrough will be recorded from the PK blood samples collected.	Approximately 1 year
Secondary	Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin	Blood samples for ATA analysis will be collected.	Approximately 1 year
Secondary	Complete response (CR) rate	CR rate is defined as the proportion of subjects achieving CR.	Up to 24 months
Secondary	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
Secondary	Rate of cystectomy	The proportion of subjects who subsequently undergo cystectomy.	Up to 5 years
Secondary	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
Secondary	Cystectomy-free survival	The time from start of study treatment to cystectomy or death due to any cause.	Up to 5 years