A Study of Adjuvant Cretostimogene Grenadenorepvec for Treatment of Intermediate Risk NMIBC Following TURBT

Study Overview
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Brief Summary
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This is a Phase 3, open-label, randomized trial designed to evaluate the RFS of TURBT followed by cretostimogene grenadenorepvec versus TURBT followed by observation for the treatment of participants with IR-NMIBC.

Detailed Description
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Participants will be randomized 1:1 to cretostimogene grenadenorepvec after TURBT (Arm A) vs observation after TURBT (Arm B). Participants in Arm A will receive an induction course and then quarterly maintenance courses of cretostimogene through Month 13, if there is no disease recurrence. Disease status will be assessed using urine cytology, complete bladder visualization (e.g., cystoscopy), and directed TURBT/biopsy (if indicated) every 3 months for the first 2 years after randomization and then every 6 months for an additional year or until disease recurrence. Participants in Arm B who recur with IR-NMIBC after TURBT and observation will be offered treatment with cretostimogene as per the treatment schedule in Arm A.

Official Title
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A Phase 3, Randomized Study of Adjuvant Cretostimogene Grenadenorepvec Versus Observation for the Treatment of Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Following Transurethral Resection of Bladder Tumor (TURBT)

Conditions
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Non Muscle Invasive Bladder Cancer, Urologic Cancer, Bladder Cancer, Urothelial Carcinoma

Intervention / Treatment
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* Drug: Cretostimogene Grenadenorepvec
* Other: n-dodecyl-B-D-maltoside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed IR-NMIBC, per American Urologic Association/Society of Urologic Oncology/National Comprehensive Cancer Network guidelines, within 12 weeks of participant randomization: Recurrent LG Ta within 12 months of prior LG or HG (HG Ta ≤ 3 cm) tumor Solitary LG Ta >3 cm tumor Multifocal LG Ta tumors Primary and solitary HG Ta ≤3 cm tumor LG T1 tumor All visible disease removed by TURBT within 12 weeks of study randomization Acceptable baseline organ function Exclusion Criteria: High-risk NMIBC (e.g., HG T1, Recurrent or multifocal HG Ta>3cm tumor(s), CIS) Low-Risk NMIBC (e.g., solitary LG Ta ≤3 cm tumor) Disease in the prostatic urethra at any time or in the upper genitourinary tract within 24 months of randomization Muscle-invasive bladder cancer, locally advanced or metastatic bladder cancer Prior treatment with any human adenovirus serotype 5 based therapy (e.g., Ad-interferon or Adstiladrin)

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 3, open-label, randomized trial designed to evaluate the RFS of TURBT followed by adjuvant cretostimogene versus TURBT alone for the treatment of participants with IR-NMIBC
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cretostimogene after TURBT<br>Following screening confirmation of IR-NMIBC and complete resection of the tumor, participants will be treated with adjuvant cretostimogene. | Drug: Cretostimogene Grenadenorepvec<br>* Engineered Oncolytic Adenovirus<br>* Other names: CG0070;Other: n-dodecyl-B-D-maltoside<br>* Transduction-enhancing agent<br>* Other names: DDM;|
| No Intervention: Observation after TURBT<br>Following screening confirmation of IR-NMIBC and complete resection of tumor, participants will enter observation. Participants who recur with IR-NMIBC after TURBT and observation will be offered treatment with cretostimogene as per the treatment schedule in Arm A. This arm will be called the Extension Arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival (RFS) | Recurrence free survival (RFS) of cretostimogene after TURBT versus observation after TURBT | 51 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival (RFS) at 12 months and 24 months | Recurrence free survival (RFS) of cretostimogene after TURBT versus observation after TURBT at 12 months and 24 months | 51 months (RFS at 12 months) and 63 months (RFS at 24 months) | 
| Incidence of Adverse Events | Safety of cretostimogene following TURBT | 52 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urology, Bladder Cancer, Non Muscle Invasive Bladder Cancer, Intermediate Risk Non Muscle Invasive Bladder Cancer, Cretostimogene Grenadenorepvec