Phase 3 Randomized Trial of Intravesical Erdafitinib Delivery System vs. Single-Agent Chemotherapy in FGFR+ Intermediate-Risk Non-Muscle Invasive Bladder Cancer

The primary objective of this Phase 3, randomized study is to compare **disease-free survival (DFS)** between two groups of participants with **FGFR+ Intermediate-risk Non-muscle Invasive Bladder Cancer (IR-NMIBC)**. Group A will receive the TAR-210 Erdafitinib Intravesical Delivery System, while Group B will receive a single-agent intravesical chemotherapy. The clinical relevance of this objective lies in determining the efficacy of the TAR-210 system in prolonging DFS, which is crucial for improving patient outcomes in this specific cancer subtype.

The clinical trial involves a total of **339 participants** diagnosed with **FGFR+ Intermediate-risk Non-muscle Invasive Bladder Cancer**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, including a histologically confirmed diagnosis of intermediate-risk non-muscle invasive bladder cancer with certain risk factors and a susceptible FGFR mutation or fusion. The trial population also includes a vulnerable population, indicating that special considerations are in place for their participation. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The selection process ensures that visible papillary disease is fully resected prior to randomization, with the absence of disease documented at screening cystoscopy.

The clinical trial is a **Phase 3, randomized, double-blind, controlled** study designed to evaluate the efficacy and safety of the TAR-210 **erdafitinib** intravesical delivery system compared to single-agent intravesical chemotherapy in participants with intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) with susceptible FGFR alterations. The trial aims to compare disease-free survival (DFS) between two groups: Group A receiving the TAR-210 erdafitinib system and Group B receiving standard intravesical chemotherapy. The trial is expected to commence recruitment on August 1, 2024, and conclude by June 28, 2028, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically confirmed diagnosis of IR-NMIBC and the presence of a susceptible FGFR mutation or fusion. Following successful screening, participants will be randomized into one of the two treatment groups. Regular follow-up visits will be scheduled to monitor treatment response, adverse events, and overall health status. The end-of-study visit will occur after the completion of the treatment period or upon early termination, which may be necessitated by disease progression, unacceptable toxicity, or withdrawal of consent.

The expected length of participant involvement is up to 12 months, with conditions for early termination including the first documented recurrence of NMIBC, disease progression, or death due to any cause. The trial will utilize a combination of chemical and biological medicinal products, with **mitomycin** and **gemcitabine** serving as comparator agents. The study will employ intravesical use as the route of administration for all investigational products. The trial's primary endpoint is the measurement of DFS, defined as the time from randomization to the first documented recurrence of NMIBC, disease progression, or death. The study is not classified as low intervention and falls under Category 2 due to its Phase 3 status.

The clinical trial involves the evaluation of three treatments for participants with intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) and susceptible FGFR alterations. The first treatment under investigation is **Mitomycin**, a chemical substance administered via **intravesical use**. The pharmaceutical form of Mitomycin is denoted as PHF675. The maximum daily dose is 40 mg, with a total treatment period of up to 12 months. Mitomycin is not a pediatric formulation and is classified as a biological medicinal product. Participant compliance with the dosing schedule will be monitored throughout the trial.

The second treatment is **Gemcitabine**, also administered via intravesical use. The pharmaceutical form is identified as PHF00230MIG. The maximum daily dose for Gemcitabine is 2000 mg, with a treatment duration of up to 12 months. This treatment is not a pediatric formulation and is classified as a chemical medicinal product. As with Mitomycin, participant adherence to the dosing regimen will be closely monitored.

The third treatment is **Erdafitinib**, marketed under the product name JNJ-42756493. This treatment is delivered using an intravesical delivery system, which includes a combination product with a device. The pharmaceutical form is a tablet, and the treatment is of chemical origin. The trial employs an intravesical delivery system and a urinary placement catheter for the administration of Erdafitinib. The maximum treatment period is 12 months. This treatment is not a pediatric formulation, and participant compliance will be assessed throughout the study.

The efficacy of the clinical trial will be assessed by comparing **disease-free survival (DFS)** between two groups: Group A and Group B. DFS is defined as the time from randomization to the first documented recurrence of non-muscle invasive bladder cancer (NMIBC) of any grade, disease progression, or death due to any cause, whichever occurs first. This primary endpoint will be measured to evaluate the effectiveness of the TAR-210 Erdafitinib Intravesical Delivery System versus single-agent intravesical chemotherapy in participants with intermediate-risk NMIBC and susceptible FGFR alterations.