Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

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

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).

Study Overview

• Status: Recruiting
• Conditions: Non-Muscle Invasive Bladder Neoplasms
• Intervention / Treatment: Drug: Erdafitinib Intravesical Delivery System

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.

• Study Type: Interventional
• Enrollment (Estimated): 235
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Active, not recruiting
      • Vancouver Prostate Centre Diamond Health Care Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Active, not recruiting
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Active, not recruiting
      • St Josephs Healthcare Hamilton
    • Toronto, Ontario, Canada, M5G 2M9
      • Completed
      • Princess Margaret Cancer Centre
• Germany
  • Dresden, Germany, 01307
    • Completed
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Duisburg, Germany, 47169
    • Completed
    • Urologicum Duisburg
  • Frankfurt am Main, Germany, 60590
    • Active, not recruiting
    • Universitatsklinikum Frankfurt
  • Herne, Germany, 44625
    • Completed
    • Marien Hospital Herne
  • Mettmann, Germany, 40822
    • Active, not recruiting
    • Urologie Neandertal Praxis Mettmann
  • Münster, Germany, 48149
    • Completed
    • Universitätsklinikum Münster
  • Ulm, Germany, 89081
    • Completed
    • Universitaetsklinikum Ulm
• Israel
  • Haifa, Israel, 3109601
    • Active, not recruiting
    • Rambam Medical Center
  • Haifa, Israel, 3436212
    • Active, not recruiting
    • Carmel Medical Center
  • Petah Tikva, Israel, 4941492
    • Active, not recruiting
    • Rabin Medical Center
  • Tel Aviv, Israel, 64239
    • Active, not recruiting
    • Tel Aviv Sourasky Medical Center
• Japan
  • Fukuoka, Japan, 810 8563
    • Active, not recruiting
    • National Hospital Organization Kyushu Medical Center
  • Kofu, Japan, 400-8506
    • Active, not recruiting
    • Yamanashi Prefectural Central Hospital
  • Osaka, Japan, 558-8558
    • Active, not recruiting
    • Osaka General Medical Center
  • Toyama, Japan, 930 0194
    • Active, not recruiting
    • Toyama University Hospital
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Completed
    • Radboud Umcn
  • Utrecht, Netherlands, 3584 CX
    • Completed
    • UMC Utrecht
• South Korea
  • Goyang-si, South Korea, 10408
    • Completed
    • National Cancer Center
  • Gwangju, South Korea, 61469
    • Active, not recruiting
    • Chonnam National University Hospital
  • Seoul, South Korea, 03080
    • Active, not recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06591
    • Completed
    • The Catholic University of Korea Seoul St Marys Hospital
  • Seoul, South Korea, 03722
    • Active, not recruiting
    • Severance Hospital Yonsei University Health System
• Spain
  • Barcelona, Spain, 08025
    • Completed
    • Fund. Puigvert
  • Barcelona, Spain, 08036
    • Active, not recruiting
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • Hosp Univ Vall D Hebron
  • Córdoba, Spain, 14004
    • Active, not recruiting
    • Hosp Reina Sofia
  • Madrid, Spain, 28041
    • Active, not recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Active, not recruiting
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28040
    • Active, not recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Valencia, Spain, 46009
    • Active, not recruiting
    • Instituto Valenciano de Oncología
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham - The Kirklin Clinic
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Recruiting
      • Urology Associates of Denver
  • Florida
    • Hialeah, Florida, United States, 33016
      • Recruiting
      • Urological Research Network
    • Largo, Florida, United States, 33771
      • Recruiting
      • Advanced Urology Institute
    • Orlando, Florida, United States, 32804
      • Completed
      • Advent Health Orlando
    • Oxford, Florida, United States, 34484
      • Completed
      • Advanced Urology Institute 1
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H Lee Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
    • Chicago Ridge, Illinois, United States, 60415
      • Recruiting
      • Associated Urological Specialists
  • Indiana
    • Greenwood, Indiana, United States, 46143
      • Recruiting
      • Urology of Indiana
    • Merrillville, Indiana, United States, 46410
      • Recruiting
      • Urologic Specialists of Northwest Indiana
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University of Kentucky
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Recruiting
      • Southern Urology LLC
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Recruiting
      • Greater Boston Urology
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Recruiting
      • Specialty Clinical Research of St Louis
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center Urology
  • New York
    • Syracuse, New York, United States, 13210
      • Recruiting
      • Associated Medical Professionals
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Completed
      • Levine Cancer Institute, Carolinas HealthCare System
  • Ohio
    • Gahanna, Ohio, United States, 43230
      • Recruiting
      • Central Ohio Urology Group
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Recruiting
      • Carolina Urologic Research Center
    • North Charleston, South Carolina, United States, 29406
      • Recruiting
      • Low Country Urology Clinics
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Recruiting
      • Urology Associates
  • Texas
    • Austin, Texas, United States, 78745
      • Recruiting
      • Urology Austin
    • San Antonio, Texas, United States, 78229
      • Completed
      • Urology San Antonio Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; 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; Erdafitinib intravesical delivery system will be administered.; Other Names: JNJ-42756493
Experimental: Part 2: Dose Expansion; 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; Erdafitinib intravesical delivery system will be administered.; Other Names: JNJ-42756493
Experimental: Part 3: RP2D Dose Expansion; Participants in 2 of the disease-specific NMIBC cohorts (cohorts 1 and 3) may be enrolled at RP2D to determine the safety, evaluate PK and preliminary clinical activity.	Drug: Erdafitinib Intravesical Delivery System; Erdafitinib intravesical delivery system will be administered.; Other Names: JNJ-42756493
Experimental: Part 4: Phase 2 Expansion; Participants with recurrent IR-NMIBC will be enrolled in this part to further evaluate the safety, efficacy, and PK of the selected RP2D.	Drug: Erdafitinib Intravesical Delivery System; Erdafitinib intravesical delivery system will be administered.; Other Names: JNJ-42756493

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 28 days
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.	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.	Up to approximately 7 years 4 months
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.	Up to approximately 7 years 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1 to 3: 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
Parts 1 to 3: 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
Parts 1 to 3: 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
Parts 1 to 3: 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
Parts 1 to 3: 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
Parts 1 to 3: 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
Parts 1 to 3: 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 approximately 7 years 4 months
Parts 1 to 3: 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 approximately 7 years 4 months
Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC	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 approximately 7 years 4 months
Part 4: Complete Response (CR) at 3 Months in Participants with IR-NMIBC	CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy at the first disease evaluation.	At Month 3
Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC	Participants with TURBT-free survival will be reported.	Up to approximately 7 years 4 months
Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity	TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that has worsened since baseline. Severity was assessed using National cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0. Severity grades 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 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	The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.	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	EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with non-muscle-invasive bladder cancer. The questionnaire is designed to supplement the QLQ C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much). Higher scores indicated greater severity.	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	The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status/quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.	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	EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with non-muscle-invasive bladder cancer. The questionnaire is designed to supplement the QLQ C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much). Higher scores indicated greater severity.	At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): July 24, 2029

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Non-Muscle Invasive Bladder Cancer (NMIBC); Muscle Invasive Bladder Cancer (MIBC)
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; erdafitinib
• Other Study ID Numbers: CR109115; 42756493BLC1003 (Other Identifier: Janssen Research & Development, LLC); 2021-004144-22 (EudraCT Number); 2023-506265-65-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No