A Phase 3, Randomized, Open-label, Multicenter Study Evaluating the Efficacy and Safety of TAR-210 Erdafitinib Intravesical Delivery System Versus Investigator’s Choice of Intravesical Chemotherapy in Participants with High-risk Non-muscle-invasive Bladder Cancer with Susceptible FGFR Alterations Who Had Received Intravesical Bacillus Calmette-Guérin (BCG)

The primary objective of this study is to compare disease-free survival (DFS) between participants receiving TAR-210 erdafitinib intravesical delivery system (Group A) and those receiving investigator's choice of intravesical chemotherapy (Group B) in patients with high-risk non-muscle-invasive bladder cancer with susceptible FGFR alterations who have previously received intravesical Bacillus Calmette-Guérin (BCG). This comparison addresses a critical clinical need in managing BCG-unresponsive or BCG-exposed non-muscle-invasive bladder cancer patients with targetable genetic alterations, where therapeutic options remain limited. The study evaluates efficacy, safety, pharmacokinetics, pharmacodynamics, tolerability, quality of life, and health economics outcomes of the targeted intravesical erdafitinib delivery system compared to standard intravesical chemotherapy regimens including gemcitabine or mitomycin.

This clinical trial enrolled a total of **130 participants** diagnosed with **high-risk non-muscle-invasive bladder cancer** with susceptible **fibroblast growth factor receptor (FGFR) alterations**. The study population included both **male** and **female** adults and elderly individuals. Participants were required to have histologically confirmed **papillary-only high-risk non-muscle-invasive bladder cancer**, defined as **high-grade Ta** or any **T1** disease without **carcinoma in situ**. All participants had documented susceptible **FGFR mutations** or **fusions** confirmed through urine or tumor tissue testing. The trial population was selected based on prior **Bacillus Calmette-Guérin (BCG)** treatment history, including those classified as **BCG-unresponsive**, **BCG-experienced**, or **BCG-intolerant**. Eligible participants had undergone complete resection of all visible tumors and demonstrated an **Eastern Cooperative Oncology Group (ECOG) performance status** of 0, 1, or 2. All participants were either ineligible for or had refused **radical cystectomy**. The study excluded individuals with **neuroendocrine** or **small cell variants** of bladder cancer.

This is a Phase 3, randomized, open-label, multicenter clinical trial evaluating the efficacy and safety of **TAR-210 erdafitinib** intravesical delivery system compared to investigator's choice of **intravesical chemotherapy** in participants with **high-risk non-muscle-invasive bladder cancer** with susceptible **FGFR alterations** who had received intravesical **Bacillus Calmette-Guérin (BCG)**. The trial employs a two-arm design in which participants are randomized to receive either the investigational product (Group A) or comparator treatment (Group B). The investigational product consists of **erdafitinib** administered via an intravesical delivery system that includes a urinary placement catheter and an intravesical delivery device. The comparator arm includes investigator's choice of intravesical chemotherapy, specifically **gemcitabine hydrochloride** or **mitomycin**, both administered via intravesical use. All investigational medicinal products contain active substances of chemical origin and are administered through the intravesical route.

The primary objective of the trial is to compare **disease-free survival (DFS)** between the two treatment groups. Participants eligible for enrollment must have histologically confirmed diagnosis of papillary-only high-risk non-muscle-invasive bladder cancer, defined as high-grade Ta or any T1 disease without carcinoma in situ. All visible tumor must be completely resected prior to randomization, and participants must have a susceptible FGFR mutation or fusion confirmed by central or local testing. Eligible participants must have received prior BCG therapy and fall into one of three categories: BCG-unresponsive, BCG-experienced, or BCG-intolerant. Participants must have an **Eastern Cooperative Oncology Group (ECOG)** performance status of 0, 1, or 2, and must be ineligible for or refusing **radical cystectomy**. The trial excludes participants with neuroendocrine or small cell variants of bladder cancer.

The estimated recruitment start date is November 28, 2025, with an estimated study completion date of March 16, 2032. The total trial duration encompasses approximately 6 years and 4 months from initiation of recruitment to final data collection. Participants will undergo screening procedures including histological confirmation, FGFR testing, and complete tumor resection prior to randomization. Following enrollment, participants will attend scheduled study visits for treatment administration, disease monitoring through cystoscopy and urine cytology, and safety assessments. Follow-up visits will continue throughout the treatment period and subsequent surveillance phase to assess disease-free survival and monitor for disease recurrence or progression. The end-of-study visit will occur upon completion of the planned follow-up period or earlier if participants meet criteria for study discontinuation. Conditions that may lead to early termination from the study include disease progression to muscle-invasive bladder cancer, development of metastatic disease, unacceptable toxicity, participant withdrawal of consent, investigator decision, or death.

The experimental medication in this clinical trial is **JNJ-42756493**, an **intravesical delivery system** containing **erdafitinib** as the active substance. The product is designated as **TAR-210 Erdafitinib Intravesical Delivery System** and represents a combination product that includes a device. The pharmaceutical form is tablet-based, administered via **intravesical use**. The investigational product is manufactured by Janssen-Cilag International N.V. and utilizes a specialized delivery mechanism consisting of two device components: an **Intravesical Delivery System** and a **Urinary Placement Catheter (UPC)**. The UPC is a sterile, single-use, transient contact medical device intended for non-surgical transurethral insertion of intravesical delivery systems into the bladder. The device has been notified through BSI Group The Netherlands B.V. and carries CE marking. The active substance erdafitinib is of chemical origin and is delivered directly to the bladder through this intravesical route of administration.

The comparator treatments in this study consist of investigator's choice of **intravesical chemotherapy**, specifically either **gemcitabine hydrochloride** or **mitomycin**. Both comparator agents are administered via **intravesical use** and are of chemical origin. Gemcitabine hydrochloride is classified under ATC code L01BC05 and may be referred to by its chemical name 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one hydrochloride. Mitomycin, also known as **mitomycin C**, is classified under ATC code L01DC03. Both comparator medications are standard chemotherapeutic agents used for intravesical treatment. The specific dosing, frequency, and duration of administration for all study treatments are determined according to the study protocol, with dosage measured in milligrams. The maximum treatment period for all study medications is defined within the protocol parameters.

This is a **Phase 3, randomized, open-label, multicenter study** designed to evaluate participants with **high-risk non-muscle-invasive bladder cancer** with susceptible **FGFR alterations** who had previously received intravesical **Bacillus Calmette-Guérin (BCG)** therapy. The study compares **disease-free survival (DFS)** between Group A receiving the experimental erdafitinib intravesical delivery system and Group B receiving investigator's choice of intravesical chemotherapy. All treatments are administered through the intravesical route, delivering the medication directly into the bladder. Participant compliance monitoring and adherence to the dosing schedule are implemented according to standard clinical trial procedures as outlined in the study protocol.

Efficacy will be assessed using **disease-free survival (DFS)** as the primary endpoint. The study aims to compare DFS between participants receiving TAR-210 erdafitinib intravesical delivery system (Group A) and those receiving investigator's choice of intravesical chemotherapy (Group B). DFS will serve as the key parameter to evaluate the therapeutic benefit of the investigational treatment in participants with high-risk **non-muscle-invasive bladder cancer** with susceptible **FGFR alterations** who have previously received intravesical **Bacillus Calmette-Guérin (BCG)**.