Phase 1/2 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non-Muscle-Invasive or Muscle-Invasive Bladder Cancer
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; 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).
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 approximately up to 7 years 4 months.
Arms & interventions
- DrugErdafitinib Intravesical Delivery System
Erdafitinib intravesical delivery system will be administered.
Outcome measures
Primary
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
Parts 1 to 3: Plasma Concentration of Erdafitinib
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
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)
Time frame: Up to approximately 7 years 4 months
Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate
Time frame: At 3 months
Parts 1 to 3: Cohort 3 and 5: Duration of CR
Time frame: Up to approximately 7 years 4 months
Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate
Time frame: Up to 8 weeks
Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)
Time frame: Up to 8 weeks
Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2
Time frame: Up to 8 weeks
Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC
Time frame: Up to approximately 7 years 4 months
Part 4: Complete Response (CR) at 3 Months in Participants with IR-NMIBC
Time frame: At Month 3
Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC
Time frame: Up to approximately 7 years 4 months
Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity
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
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
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
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)
Eligibility criteria
Study locations (25)
University of Alabama at Birmingham - The Kirklin Clinic
Birmingham, Alabama, 35294
University of Southern California
Los Angeles, California, 90033
Urology Associates of Denver
Lone Tree, Colorado, 80124
Urological Research Network
Hialeah, Florida, 33016
Advanced Urology Institute
Largo, Florida, 33771
Advent Health Orlando
Orlando, Florida, 32804
Advanced Urology Institute 1
Oxford, Florida, 34484
H Lee Moffitt Cancer Center
Tampa, Florida, 33612
Northwestern University
Chicago, Illinois, 60611
Associated Urological Specialists
Chicago Ridge, Illinois, 60415
Urology of Indiana
Greenwood, Indiana, 46143
Urologic Specialists of Northwest Indiana
Merrillville, Indiana, 46410
University of Kentucky
Lexington, Kentucky, 40506
Southern Urology LLC
Lafayette, Louisiana, 70508
Greater Boston Urology
Plymouth, Massachusetts, 02360
Specialty Clinical Research of St Louis
St Louis, Missouri, 63141
Hackensack University Medical Center Urology
Hackensack, New Jersey, 07601
Associated Medical Professionals
Syracuse, New York, 13210
Levine Cancer Institute, Carolinas HealthCare System
Charlotte, North Carolina, 28204
Central Ohio Urology Group
Gahanna, Ohio, 43230
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Low Country Urology Clinics
North Charleston, South Carolina, 29406
Urology Associates
Nashville, Tennessee, 37209
Urology Austin
Austin, Texas, 78745
Urology San Antonio Research
San Antonio, Texas, 78229