study of erdafitinib intravesical delivery system for localized bladder cancer

Conditions: Urinary Bladder Neoplasms; Receptors, Fibroblast Growth Factor

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).

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 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

Keywords: non-muscle-invasive bladder cancer (nimbc) muscle-invasive bladder cancer (mibc)