Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 1

Conditions: Urinary Bladder Neoplasms; Receptors, Fibroblast Growth Factor

Treatments: Drug: Erdafitinib Intravesical Delivery System

Study type: Interventional

Funder types: Industry

Identifiers

NCT05316155

CR109115

42756493BLC1003 (Other Identifier)

2021-004144-22 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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112 participants in 3 patient groups

Part 1: Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: Erdafitinib Intravesical Delivery System

Part 2: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: Erdafitinib Intravesical Delivery System

Part 3: RP2D Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: Erdafitinib Intravesical Delivery System