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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Enfortumab vedotin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enfortumab vedotin: Dose escalation cohort<br>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<br>* Given into the bladder (intravesically)<br>* Other names: PADCEV, ASG-22CE, ASG-22ME;|
| Experimental: Enfortumab vedotin: Dose expansion cohort<br>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<br>* Given into the bladder (intravesically)<br>* Other names: PADCEV, ASG-22CE, ASG-22ME;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics