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

• ClinicalTrials.gov Identifier: NCT05014139
• Recruitment Status: Recruiting
• First Posted: August 20, 2021
• Last Update Posted: May 3, 2023
• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborator: Seagen Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information

• First Submitted Date: August 16, 2021
• First Posted Date: August 20, 2021
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: December 7, 2021
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2021)

• Incidence of adverse events (AEs) [ Time Frame: Approximately 1 year ]
  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.
• Incidence of laboratory abnormalities [ Time Frame: Approximately 1 year ]
  To be summarized using descriptive statistics.
• Incidence of dose limiting toxicities (DLTs) [ Time Frame: Approximately 7 weeks ]
  To be summarized using descriptive statistics.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 16, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
• Official Title: A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)

Brief 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.

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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: Enfortumab vedotin

Given into the bladder (intravesically)

Other Name: PADCEV, ASG-22CE, ASG-22ME

Study Arms

• 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.
  Intervention: Drug: Enfortumab vedotin
• 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.
  Intervention: Drug: Enfortumab vedotin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 16, 2021): 58
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2028
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Seagen, Inc. Trial Information Support; 866-333-7436; clinicaltrials@seagen.com

• Listed Location Countries: Canada, France, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05014139
• Other Study ID Numbers: SGN22E-004; EV-104 ( Other Identifier: Seagen, Inc. )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Astellas Pharma Global Development, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Seagen Inc.

Investigators

• Study Director: Janet Trowbridge, MD; Seagen Inc.

• PRS Account: Astellas Pharma Inc
• Verification Date: May 2023