Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

Phase 2Active Not RecruitingNCT05316155

Janssen Research & Development, LLC235 enrolled

Overview

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).

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

235

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

Erdafitinib Intravesical Delivery SystemDRUG

Erdafitinib intravesical delivery system will be administered.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (59)

Outcomes

Primary Outcomes

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 Outcomes

Parts 1 to 3: Plasma Concentration of Erdafitinib

Plasma concentration of Erdafitinib will be reported.

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

Data from ClinicalTrials.gov

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University of Alabama at Birmingham - The Kirklin Clinic

Birmingham, Alabama, United States

University of Southern California

Los Angeles, California, United States

Urology Associates of Denver

Lone Tree, Colorado, United States

Urological Research Network

Hialeah, Florida, United States

Advanced Urology Institute

Largo, Florida, United States

Advent Health Orlando

Orlando, Florida, United States

Advanced Urology Institute 1

Oxford, Florida, United States

H Lee Moffitt Cancer Center

Tampa, Florida, United States

Northwestern University

Chicago, Illinois, United States

Associated Urological Specialists

Chicago Ridge, Illinois, United States

...and 49 more locations

Urine concentration of Erdafitinib will be reported.

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)

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.

Time frame: Up to approximately 7 years 4 months

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.

Time frame: At 3 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.

Time frame: Up to approximately 7 years 4 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).

Time frame: 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.

Time frame: 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.

Time frame: Up to 8 weeks

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

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

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.

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

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.

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

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.

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)