Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects With High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC)

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of FE 999326 in Japanese subjects with high-grade, BCG unresponsive NMIBC.

Official Title
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A Phase 3, Open Label Trial to Evaluate the Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects With High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC)

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: FE 999326


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only Ta/T1 high-grade disease with concomitant CIS or Ta/T1 high-grade disease without concomitant CIS Subjects who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. Life expectancy >2 years, in the opinion of the investigator Eastern Cooperative Oncology Group (ECOG) status 2 or less Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra Subjects with prostate cancer on active surveillance at low risk for progression, defined as prostate-specific antigen (PSA) <10 ng/dL Exclusion Criteria: Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease presented at the screening visit. Current systemic therapy for bladder cancer Current or prior investigational treatment for BCG unresponsive NMIBC or any other investigational drug within 1 month prior to screening Current or prior pelvic external beam radiotherapy within 5 years of entry Use of other adenovirus vector medications, including COVID-19 vaccines, within 2 weeks before and after instillation History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤pT2 upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Subjects who cannot hold instillation for 1 hour Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation Intravesical therapy within 8 weeks prior to beginning trial treatment, with the exception of: Cytotoxic agents when administered as a single instillation immediately following a TURBT procedure Previous intravesical BCG therapy Systemic immunosuppressive therapy within 3 months prior to screening

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FE 999326<br> | Drug: FE 999326<br>* 75 mL FE 999326 (3 x 10^11 vp/mL) of sterile suspension instilled once every 3 months into the bladder via a urinary catheter<br>* Other names: nadofaragene firadenovec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whether or not a subject with CIS (with or without concomitant high-grade Ta or T1 papillary disease) responds to treatment, defined as complete response at any time after first administration of FE 999326 | A subject with CIS (with or without concomitant high-grade Ta or T1 papillary disease) has achieved a complete response at an efficacy assessment if urine cytology is negative and there are no lesions on cystoscopy. If biopsy of the bladder is performed, this must be negative. | At Month 12 assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of complete response in subjects with CIS (with or without concomitant high-grade Ta or T1 papillary disease) who show a complete response at any time after first administration of FE 999326 |  | Up to 5 years | 
| Whether or not a subject with high-grade Ta or T1 papillary disease (without concomitant CIS) responds to treatment, defined as absence of recurrence of high-grade disease |  | Up to 4 years | 
| Duration of event-free survival in subjects with high-grade Ta or T1 papillary disease (without concomitant CIS) and in subjects with CIS (with or without papillary disease) |  | Up to 5 years | 
| Incidence of cystectomy |  | Up to 4 years | 
| Time to cystectomy |  | Up to 4 years | 
| Overall survival |  | Up to 5 years | 
| Concentration of FE 999326-specific DNA levels in urine |  | Up to day 1 of month 4 after start of treatment; and 3, 6, 9 and 12 months after last dose (up to 5 years after start of treatment) | 
| Type, incidence, relatedness and severity of treatment emergent adverse events |  | Up to 5 years |