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RecruitingInterventionalPhase 1/Phase 2

Phase 1/2 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non-Muscle-Invasive or Muscle-Invasive Bladder Cancer

NCT ID: NCT05316155Sponsor: Janssen Research & Development, LLCLast updated: 2026-06-05

Summary

The purpose of the study in Part 1 (dose escalation) and in Part 2 (dose expansion) is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) and evaluate preliminary clinical efficacy. Part 3 (dose expansion) will confirm safety and preliminary clinical activity at the RP2D. Part 4 (RP2D expansion; MoonRISe-2) will assess the overall complete response (CR) in participants with intermediate-risk-non-muscle invasive bladder cancer (IR-NMIBC; means the cancer cells are only in the bladder's inner lining).

Detailed description

Bladder cancer is one of the most common malignancy worldwide, and non-muscle invasive (NMIBC) requires intensive regimens of frequent monitoring and 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 approximately up to 7 years 4 months.

Arms & interventions

  • DrugErdafitinib Intravesical Delivery System

    Erdafitinib intravesical delivery system will be administered.

Outcome measures

Primary

  • Parts 1 to 3: 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.

    Time frame: Up to approximately 7 years 4 months

  • Parts 1 to 3: 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.

    Time frame: Up to approximately 7 years 4 months

  • Part 1: 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.

    Time frame: Up to 28 days

  • Part 4: Overall Complete Response (CR) in Participants with Intermediate Risk-Non-Muscle Invasive Bladder Cancer (IR-NMIBC)

    Overall CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy.

    Time frame: Up to approximately 7 years 4 months

Secondary

  • Parts 1 to 3: Plasma Concentration of Erdafitinib

    Time frame: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks

  • Parts 1 to 3: Urine Concentration of Erdafitinib

    Time frame: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks

  • Parts 1 to 3: Cohorts 1 and 2: Recurrence-Free Survival (RFS)

    Time frame: Up to approximately 7 years 4 months

  • Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate

    Time frame: At 3 months

  • Parts 1 to 3: Cohort 3 and 5: Duration of CR

    Time frame: Up to approximately 7 years 4 months

  • Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate

    Time frame: Up to 8 weeks

  • Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)

    Time frame: Up to 8 weeks

  • Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2

    Time frame: Up to 8 weeks

  • Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC

    Time frame: Up to approximately 7 years 4 months

  • Part 4: Complete Response (CR) at 3 Months in Participants with IR-NMIBC

    Time frame: At Month 3

  • Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC

    Time frame: Up to approximately 7 years 4 months

  • Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity

    Time frame: Up to approximately 7 years 4 months

  • Part 4: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score

    Time frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)

  • Part 4: Change from Baseline in European Organization for the Research and Treatment of Cancer Non-Muscle Invasive Bladder Cancer (EORTC-QLQ-NMIBC 24) Score

    Time frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)

  • Part 4: Percentage of Participants With Clinically Meaningful Change From Baseline in EORTC-QLQ-C30 Scores

    Time frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)

  • Part 4: Percentage of Participants With Clinically Meaningful Change From Baseline in EORTC-QLQ-NMIBC24 Scores

    Time frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: Parts 1-3: * Muscle-invasive or recurrent, non-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 Part 4: * Have histologically confirmed diagnosis of recurrent Intermediate-risk-non-muscle invasive bladder cancer (IR-NMIBC) Ta LG tumors * Must not have undergone tumor debulking or selective ablation of visible lesions; partial tumor biopsy to confirm diagnosis and provide tissue for biomarker testing is permitted as long as remaining tumor is at least 5 millimeter (mm) in size * Must submit tissue and urine for FGFR testing * Can have a prior or concurrent second malignancy which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment Exclusion Criteria: Parts 1-3: * 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 Part 4: * Histologically confirmed diagnosis of T1 NMIBC, HR NMIBC (HG/G2 or HG/G3 or CIS) or MIBC, locally advanced, non-resectable, or metastatic urothelial carcinoma at any time prior to enrollment. Previous high grade (HG) disease is accepted as long as diagnosis date is greater than or equal to (\>=5) years ago and there is documentation of low grade (LG) Ta thereafter * Known allergies, hypersensitivity, or intolerance to any study component or its excipients * Has a current diagnosis of newly diagnosed IR-NMIBC * Received an investigational treatment for bladder cancer after Transurethral Resection of the Bladder Tumor (TURBT) for the current NMIBC diagnosis or within 4 weeks or the agent/therapy washout period, whichever is longer, before the planned first dose of study treatment, or is currently enrolled in an investigational study * Evidence of current bladder perforation by cystoscopy or imaging

Study locations (25)

University of Alabama at Birmingham - The Kirklin Clinic

Birmingham, Alabama, 35294

Recruiting

University of Southern California

Los Angeles, California, 90033

Recruiting

Urology Associates of Denver

Lone Tree, Colorado, 80124

Recruiting

Urological Research Network

Hialeah, Florida, 33016

Recruiting

Advanced Urology Institute

Largo, Florida, 33771

Recruiting

Advent Health Orlando

Orlando, Florida, 32804

Completed

Advanced Urology Institute 1

Oxford, Florida, 34484

Completed

H Lee Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting

Northwestern University

Chicago, Illinois, 60611

Recruiting

Associated Urological Specialists

Chicago Ridge, Illinois, 60415

Recruiting

Urology of Indiana

Greenwood, Indiana, 46143

Recruiting

Urologic Specialists of Northwest Indiana

Merrillville, Indiana, 46410

Recruiting

University of Kentucky

Lexington, Kentucky, 40506

Recruiting

Southern Urology LLC

Lafayette, Louisiana, 70508

Recruiting

Greater Boston Urology

Plymouth, Massachusetts, 02360

Recruiting

Specialty Clinical Research of St Louis

St Louis, Missouri, 63141

Recruiting

Hackensack University Medical Center Urology

Hackensack, New Jersey, 07601

Recruiting

Associated Medical Professionals

Syracuse, New York, 13210

Recruiting

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, 28204

Completed

Central Ohio Urology Group

Gahanna, Ohio, 43230

Recruiting

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572

Recruiting

Low Country Urology Clinics

North Charleston, South Carolina, 29406

Recruiting

Urology Associates

Nashville, Tennessee, 37209

Recruiting

Urology Austin

Austin, Texas, 78745

Recruiting

Urology San Antonio Research

San Antonio, Texas, 78229

Completed