Phase 1/2 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non-Muscle-Invasive or Muscle-Invasive Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 235
- 试验地点
- 155
- 主要终点
- Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Part 2: Dose Expansion
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.
干预措施: Erdafitinib Intravesical Delivery System (Drug)
Part 3: RP2D Dose Expansion
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.
干预措施: Erdafitinib Intravesical Delivery System (Drug)
Part 4: Phase 2 Expansion
Participants with recurrent IR-NMIBC will be enrolled in this part to further evaluate the safety, efficacy, and PK of the selected RP2D.
干预措施: Erdafitinib Intravesical Delivery System (Drug)
Part 1: Dose Escalation
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.
干预措施: Erdafitinib Intravesical Delivery System (Drug)
结局指标
主要结局
Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
时间窗: Up to 28 days
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.
Parts 1 to 3: Number of Participants with Adverse Events (AEs)
时间窗: Up to approximately 7 years 4 months
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.
Parts 1 to 3: Number of Participants with AEs by Severity
时间窗: Up to approximately 7 years 4 months
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.
Part 4: Overall Complete Response (CR) in Participants with Intermediate Risk-Non-Muscle Invasive Bladder Cancer (IR-NMIBC)
时间窗: Up to approximately 7 years 4 months
Overall CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy.
次要结局
- Parts 1 to 3: Urine Concentration of Erdafitinib(Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks)
- Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate(At 3 months)
- Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2(Up to 8 weeks)
- Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate(Up to 8 weeks)
- Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)(Up to 8 weeks)
- Parts 1 to 3: Plasma Concentration of Erdafitinib(Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks)
- Parts 1 to 3: Plasma Concentration of Erdafitinib(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(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)(Up to 5 years 11 months)
- Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate(At 3 months)
- Parts 1 to 3: Cohort 3 and 5: Duration of CR(Up to 5 years 11 months)
- Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate(Up to 8 weeks)
- Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)(Up to 8 weeks)
- Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2(Up to 8 weeks)
- Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC(Up to 5 years 11 months)
- Part 4: Complete Response (CR) in Participants with IR-NMIBC(At Month 3)
- Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC(Up to 5 years 11 months)
- Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity(Up to 5 years 11 months)
- Parts 1 to 3: Cohorts 1 and 2: Recurrence-Free Survival (RFS)(Up to approximately 7 years 4 months)
- Parts 1 to 3: Cohort 3 and 5: Duration of CR(Up to approximately 7 years 4 months)
- Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC(Up to approximately 7 years 4 months)
- Part 4: Complete Response (CR) at 3 Months in Participants with IR-NMIBC(At Month 3)
- Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC(Up to approximately 7 years 4 months)
- Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity(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(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(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(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(At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months))