Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

Study Overview
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Brief Summary
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The purpose of the study in Part 1 (dose escalation) is to determine the recommended Phase 2 dose(s) (RP2D[s]) and in Part 2 (dose expansion) is to determine the safety of Erdafitinib Intravesical Delivery System administered at the RP2D(s).

Detailed Description
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Bladder cancer is the most common malignancy worldwide where non-muscle invasive (NMIBC), requiring intensive regimens of frequent monitoring, local resection (transurethral resection of bladder [TURBT]). This study enrolls participants with non-muscle invasive or muscle invasive bladder cancer with activating fibroblast growth factor receptor (FGFR) mutations or fusions. Erdafitinib is a pan-FGFR inhibitor with demonstrated clinical activity when administered orally in patients with solid tumors, including bladder cancer, with FGFR genetic alterations. The Erdafitinib intravesical delivery system is designed to provide release of Erdafitinib in the bladder to treat localized bladder cancer, while reducing systemic toxicities. The study consists of a screening phase, a treatment phase, and a follow-up phase. Total duration of the study is 5 years 3 months.

Official Title
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Phase 1 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non- Muscle-Invasive or Muscle-Invasive Bladder Cancer and Selected FGFR Mutations or Fusions

Conditions
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Urinary Bladder Neoplasms, Receptors, Fibroblast Growth Factor

Intervention / Treatment
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* Drug: Erdafitinib Intravesical Delivery System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent, non-muscle-invasive or muscle-invasive urothelial carcinoma of the Bladder For selected Cohorts: Activating tumor pan-fibroblast growth factor receptor (FGFR) mutation or fusion, as determined by local or central testing, approved by the sponsor prior to the start of study treatment. Local tissue-based results (if already existing) from next-generation sequencing (NGS) or polymerase chain reaction (PCR) tests performed in Clinical Laboratory Improvement Amendments (CLIA) -certified or equivalent laboratories, or results from commercially available PCR or NGS tests Cohorts 1 and 2: Bacillus Calmette-Guérin (BCG) experienced, or participants with no BCG experience because BCG was not available as a treatment option in the participant's location within the previous 2 years and is currently unavailable. Participants who received an abbreviated course of BCG due to toxicity are still eligible Cohort 1 only: Refuses or is not eligible for radical cystectomy (RC) Cohorts 2 and 4: Willing and eligible for RC Exclusion Criteria: Concurrent extra-vesical (that is, urethra, ureter, renal pelvis) transitional cell carcinoma of the urothelium Prior treatment with an pan-fibroblast growth factor receptor (FGFR) inhibitor Received pelvic radiotherapy <=6 months prior to the planned start of study treatment. If received pelvic radiotherapy greater than (>)6 months prior to the start of study treatment, there must be no cystoscopic evidence of radiation cystitis Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe use of Erdafitinib intravesical delivery system Indwelling urinary catheter. Intermittent catheterization is acceptable

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Participants with recurrent, bacillus Calmette-Guerin (BCG)-experienced high risk papillary-only Non-Muscle-Invasive Bladder Cancer (NMIBC), refusing or ineligible for radical cystectomy or with recurrent, intermediate-risk NMIBC will receive Erdafitinib Intravesical Delivery System. The dose will be escalated to determine preliminary recommended phase 2 dose(s) (RP2D[s]) for Part 2. | Drug: Erdafitinib Intravesical Delivery System<br>* Erdafitinib intravesical delivery system will be administered.<br>* Other names: JNJ-42756493;|
| Experimental: Part 2: Dose Expansion<br>Participants in each of 5 disease-specific NMIBC or MIBC cohorts may be enrolled at one or more dose levels that have been determined to be safe in Part 1. | Drug: Erdafitinib Intravesical Delivery System<br>* Erdafitinib intravesical delivery system will be administered.<br>* Other names: JNJ-42756493;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 5 years 3 months | 
| Number of Participants with AEs by Severity | Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. | Up to 5 years 3 months | 
| Number of Participants with Dose-limiting Toxicity (DLT) | Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of Erdafitinib | Plasma concentration of Erdafitinib will be reported. | Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks | 
| Urine Concentration of Erdafitinib | Urine concentration of Erdafitinib will be reported. | Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks | 
| Cohorts 1 and 2: Recurrence-Free Survival (RFS) | RFS is defined as the time from start of treatment to the first detection of any new high-grade bladder cancer or upper tract urothelial carcinoma or positive urine cytology. | Up to 5 years 3 months | 
| Cohort 3 and 5: Complete Response (CR) Rate | CR is defined as the absence of urothelial carcinoma by cystoscopy, confirmed pathologically at first assessment, and negative urine cytology. | At 3 months | 
| Cohort 3 and 5: Duration of CR | Duration of CR is defined as the time from first documentation of CR until the date of documented recurrence or progression, or death, whichever comes first. | Up to 5 years 3 months | 
| Cohort 4: Pathological Complete Response (pCR) Rate | pCR rate is defined as percentage of participants with no pathologic evidence of intravesical disease (pT0) and no pathologic evidence of nodal involvement (pN0). | Up to 8 weeks | 
| Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0) | pT0 rate is defined as percentage of participants with no Pathologic Evidence of Intravesical Disease. | Up to 8 weeks | 
| Cohort 4: Rate of downstaging to Less than (<) pT2 | Rate of downstaging to <pT2 is defined as percentage of participants with pT stage <2. | Up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Muscle-Invasive Bladder Cancer (NIMBC), Muscle-Invasive Bladder Cancer (MIBC)