Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Urinary Bladder Neoplasms; Receptors, Fibroblast Growth Factor
• 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 5 years 3 months.

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Germany
  • Frankfurt am Main, Germany, 60590
    • Recruiting
    • Universitätsklinikum Frankfurt
  • Herne, Germany, 44625
    • Recruiting
    • Marien Hospital Herne
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster
  • Ulm, Germany, 89081
    • Recruiting
    • Universitaetsklinikum Ulm
• Korea, Republic of
  • Goyang-Si, Korea, Republic of, 10408
    • Recruiting
    • National Cancer Center
  • Gwangju, Korea, Republic of, 61469
    • Recruiting
    • Chonnam National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea Seoul St. Mary's Hospital
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Completed
    • Radboud Umcn
  • Utrecht, Netherlands, 3584 CX
    • Completed
    • UMC Utrecht
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • Barcelona, Spain, 08025
    • Completed
    • Fund. Puigvert
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute, Carolinas HealthCare System
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Recruiting
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Recruiting
      • Urology Associates
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • 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:

• 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

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

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

3

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

What is the study measuring?

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
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
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
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

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): March 31, 2028

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): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Muscle-Invasive Bladder Cancer (MIBC); Non-Muscle-Invasive Bladder Cancer (NIMBC)
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: CR109115; 42756493BLC1003 (Other Identifier: Janssen Research & Development, LLC); 2021-004144-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/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