A Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)

Janssen Research & Development, LLC107 enrolled

Overview

The purpose of this study is to evaluate recurrence-free survival (RFS) in participants treated with erdafitinib vs Investigator's Choice, for participants with high-risk non-muscle-invasive bladder cancer (NMIBC) who harbor fibroblast growth factor receptor (FGFR) mutations or fusions, and who recurred after bacillus calmette-guerin (BCG) therapy.

This study enrolls participants with high risk NMIBC and FGFR mutations or fusions. Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) 1-4 inhibitor with demonstrated clinical activity in participants with solid tumors, including urothelial carcinoma, with alterations in the FGFR pathway. In Cohort 1, participants will be randomized to erdafitinib or to Investigators Choice (intravesical gemcitabine or intravesical mitomycin C \[MMC\] or hyperthermic MMC). The study consists of screening period, treatment phase, follow-up phase, and long-term extension phase.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

107

Conditions

Urinary Bladder Neoplasms

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed * Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions * Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants * Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only) * Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1 * Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study * A woman of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3) * Adequate bone marrow, liver, and renal function as specified in the protocol Exclusion Criteria: * Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder * Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder * Prior treatment with an FGFR inhibitor * Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy * Current central serous retinopathy or retinal pigment epithelial detachment of any grade

Locations (150)

Urological Associates of Southern Arizona, P.C.

Tucson, Arizona, United States

USC Institute of Urology

Los Angeles, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Urological Research Network

Hialeah, Florida, United States

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Cohort 1: Recurrence-Free Survival (RFS)

RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or carcinoma in situ \[CIS\]), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and computed tomography (CT)/ magnetic resonance imaging (MRI) urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment. The Kaplan-Meier method was used to estimate the distribution of overall RFS for each treatment group.

Time frame: From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months

Secondary Outcomes

Cohort 1: Recurrence-Free Survival Rate at 6 Months and 12 Months

RFS rate was the proportion of participants who were recurrence-free and alive based on Kaplan-Meier estimates. RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or CIS), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and CT/ MRI urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment.

Time frame: At Month 6 and Month 12

Cohort 1: Time to Progression

Time to progression (TTP) was defined as the time from the date of randomization until the date of first documented evidence of any of the following: disease progression (PD) or death. PD included development of or increase in stage to lamina propria invasion (for example- increase from Ta to T1), development of or increase in stage to muscle-invasive disease (stage greater than or equal to \[\>=\] T2), development of or increase in stage to lymph node (N+) or distant metastasis (M1) disease (participants must have previously been diagnosed with N0 and/or M0 disease), increase in tumor grade from low to high (including CIS).

Time frame: From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months

Cohort 1: Overall Survival

Overall survival was defined as the time from the date of randomization to the date of the participant's death due to any cause.

Time frame: From randomization (Cycle 1 Day 1, pre-dose) up to 48.2 months

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were the events between first dose of study drug and up to 30 (+7 days) days after last dose or before start of subsequent anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure (OM).

Time frame: From start of treatment (Day 1) up to 25.2 months

Plasma Concentrations of Erdafitinib

Plasma concentrations of erdafitinib were reported. Plasma samples were analyzed using liquid chromatography/mass spectrometry method.

Time frame: All cohorts: Pre-dose on Cycle 1 Day 14, pre-dose and 3 hours post-dose on Cycle 2 Day 1 (each cycle was of 28 days)