Clinical trial NCT05316155: Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer
Official title: Phase 1/2 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non-Muscle-Invasive or Muscle-Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Urinary Bladder Neoplasms
Receptors, Fibroblast Growth Factor
Keywords: Non-Muscle-Invasive Bladder Cancer (NIMBC)
Muscle-Invasive Bladder Cancer (MIBC)
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 262
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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) 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 5 years 11 months.

Eligibility criteria: 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
* Known allergies, hypersensitivity, or intolerance to any study component or its excipients
* Has a current diagnosis of primary 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

Primary outcomes:
measure: Parts 1 to 3: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 5 years 11 months
measure: Parts 1 to 3: Number of Participants with AEs by Severity
timeFrame: Up to 5 years 11 months
measure: Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 28 days
measure: Part 4: Overall Complete Response (CR) in Participants with Intermediate Risk-Non-Muscle Invasive Bladder Cancer (IR-NMIBC)
timeFrame: Up to 5 years 11 months
Secondary outcomes:
measure: Parts 1 to 3: Plasma Concentration of Erdafitinib
timeFrame: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
measure: Parts 1 to 3: Urine Concentration of Erdafitinib
timeFrame: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
measure: Parts 1 to 3: Cohorts 1 and 2: Recurrence-Free Survival (RFS)
timeFrame: Up to 5 years 11 months
measure: Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate
timeFrame: At 3 months
measure: Parts 1 to 3: Cohort 3 and 5: Duration of CR
timeFrame: Up to 5 years 11 months
measure: Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate
timeFrame: Up to 8 weeks
measure: Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)
timeFrame: Up to 8 weeks
measure: Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2
timeFrame: Up to 8 weeks
measure: Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC
timeFrame: Up to 5 years 11 months
measure: Part 4: Complete Response (CR) in Participants with IR-NMIBC
timeFrame: At Month 3
measure: Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC
timeFrame: Up to 5 years 11 months
measure: Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity
timeFrame: Up to 5 years 11 months
measure: Part 4: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score
timeFrame: Up to 5 years 11 months
measure: 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
timeFrame: Up to 5 years 11 months
measure: Part 4: Percentage of Participants With Significant Change From Baseline in EORTC-QLQ-C30 Scores
timeFrame: Up to 5 years 11 months
measure: Part 4: Percentage of Participants With Significant Change From Baseline in EORTC-QLQ-NMIBC24 Scores
timeFrame: Up to 5 years 11 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Lone Tree
country: United States
facility: Urology Associates of Denver
state: Colorado
city: Hialeah
country: United States
facility: Urological Research Network
state: Florida
city: Largo
country: United States
facility: Advanced Urology Institute
state: Florida
city: Oxford
country: United States
facility: Advanced Urology Institute
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Chicago Ridge
country: United States
facility: Associated Urological Specialists
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Greenwood
country: United States
facility: Urology of Indiana
state: Indiana
city: Merrillville
country: United States
facility: Urologic Specialists of Northwest Indiana
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Lafayette
country: United States
facility: Southern Urology LLC
state: Louisiana
city: Plymouth
country: United States
facility: Greater Boston Urology
state: Massachusetts
city: Syracuse
country: United States
facility: Associated Medical Professionals
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas HealthCare System
state: North Carolina
city: Gahanna
country: United States
facility: Central Ohio Urology Group
state: Ohio
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: North Charleston
country: United States
facility: Low Country Urology Clinics
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Vancouver
country: Canada
facility: Vancouver Prostate Centre Diamond Health Care Centre
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Frankfurt am Main
country: Germany
facility: Universitatsklinikum Frankfurt
city: Herne
country: Germany
facility: Marien hospital Herne
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Toyama-shi
country: Japan
facility: Toyama University Hospital
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Nijmegen
country: Netherlands
facility: Radboud Umcn
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Barcelona
country: Spain
facility: Fund. Puigvert
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: