Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC
- Conditions
- High-Risk Non-Muscle-Invasive Bladder Cancer
- Interventions
- Registration Number
- NCT06567743
- Lead Sponsor
- CG Oncology, Inc.
- Brief Summary
This is a Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk Non-Muscle-Invasive Bladder Cancer.
- Detailed Description
In Cohort A, up to 125 participants will be enrolled with pathologically confirmed, high-risk high-grade non-muscle invasive bladder cancer (NMIBC) NMIBC (i.e., CIS with or without concomitant Ta or T1 disease OR HG Ta/T1 disease without CIS) which is naïve to Bacillus Calmette-Guerin (BCG) treatment. Participants with CIS with or without concomitant Ta/T1 NMIBC at baseline will be randomized 1:1 to receive cretostimogene via the current (Arm 1) or an alternative instillation procedure (Arm 2). Participants with papillary-only high-risk NMIBC (i.e., HG Ta/T1 without CIS) at baseline (Arm 3) will receive cretostimogene via the alternative instillation procedure.
In Cohort B, up to 150 participants will be enrolled with pathologically confirmed, high-risk high-grade NMIBC (i.e., CIS with or without concomitant Ta or T1 disease OR HG Ta/T1 disease without CIS) which has previously been exposed to BCG treatment. Participants with CIS-containing pathology at baseline will be recruited into Arm 1 and participants with papillary-only pathology at baseline will be recruited into Arm 2. Both Cohort B Arms 1 and 2 will receive cretostimogene via the alternative instillation procedure.
In Cohort CX, up to 50 participants will be enrolled with pathologically confirmed, high-risk high-grade NMIBC (i.e., CIS with or without concomitant Ta or T1 disease OR HG Ta/T1 disease without CIS) which has previously been exposed to or is unresponsive to BCG treatment. Participants will be randomized 1:1 to receive cretostimogene and gemcitabine either concurrently or sequentially.
In all cohorts, study treatment will be administered as a weekly induction course for the first 6 weeks with a reinduction course administered to patients who have CIS and/or high-grade Ta disease at the 3-month evaluation. Following induction, if no high-grade disease is detected, maintenance treatment will begin. This consists of a cycle of three weekly treatments every three months during the first year, and every six months during the second year, with an optional extension to the third year following the same six-month schedule.
Disease status will be assessed using urine cytology, complete bladder visualization (e.g., cystoscopy), upper tract assessment and directed resection/biopsy (if indicated) every 3 months for the first 2 years and then every 6 months for a further 2 years or until disease recurrence.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 325
- Pathologically confirmed BCG-naïve high-risk high-grade NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
- All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
- Acceptable baseline organ function.
Cohort B Key Inclusion Criteria:
- Pathologically confirmed BCG-exposed high-risk high-grade NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
- All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
- Acceptable baseline organ function.
Cohort CX Inclusion Criteria
- Pathologically confirmed high-risk high-grade BCG-unresponsive or BCG-exposed NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
- All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
- Acceptable baseline organ function.
Key Exclusion Criteria (Both Cohorts):
- Current or past history of muscle-invasive, locally advanced or metastatic bladder cancer.
- High-grade urothelial carcinoma in the upper urinary tract or prostatic urethra within 24 months or T2 in upper tract within 48 months or any history of locally advanced/ nodal or metastatic disease in the upper urinary tract.
- Significant immunodeficiency.
- Pregnant or breastfeeding.
- Cohort CX Only: serial intravesical gemcitabine within 24 months
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental: Cohort A, Arm 1 Cretostimogene Grenadenorepvec Cretostimogene (1 x 1012 vp) will be administered intravesically via the current instillation method Experimental: Cohort A, Arm 2 Cretostimogene Grenadenorepvec Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. Experimental: Cohort A, Arm 3 Cretostimogene Grenadenorepvec Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. Experimental: Cohort B, Arm 1 Cretostimogene Grenadenorepvec Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. Experimental: Cohort B, Arm 2 Cretostimogene Grenadenorepvec Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. Experimental: Cohort CX, Arm 1 Cretostimogene Grenadenorepvec At all treatment visits cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method followed by gemcitabine instilled intravesically Experimental: Cohort CX, Arm 2 Cretostimogene Grenadenorepvec Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method for two consecutive weeks, followed by gemcitabine administered intravesically in the third week on a cyclic 2:1 visit schedule basis
- Primary Outcome Measures
Name Time Method Cohort B (Arm 2): High-Grade Event-Free Survival 48 months Determine the High-Grade Event-Free Survival following treatment with cretostimogene in participants with BCG-exposed high-grade Ta/T1 papillary disease without CIS at baseline.
Cohort CX (Arms 1 and 2): High-Grade Event-Free Survival 48 months Determine the High-Grade Event-Free Survival following treatment with cretostimogene in participants with BCG-exposed or BCG-unresponsive high-grade NMIBC.
Cohort CX (Arms 1 and 2): Safety 48 months Determine the safety of concurrent cretostimogene and gemcitabine and sequential cretostimogene and gemcitabine.
Cohort A (Arm 1 and 2): Complete response rate At 11 and 24 weeks Determine the complete response rate at any time following treatment with cretostimogene in participants with BCG-naïve CIS with or without concomitant high-grade Ta or T1 disease at baseline
Cohort A (Arm 3): High- Grade Event-Free Survival 48 months Determine the High-Grade Event-Free Survival following treatment with cretostimogene in participants with BCG-naïve HG Ta/T1 disease without concomitant CIS at baseline.
Cohort B (Arm 1): Complete response rate At 11 and 24 weeks Determine the complete response rate at any time following treatment with cretostimogene in participants with BCG-exposed CIS with or without concomitant high-grade Ta or T1 disease at baseline.
- Secondary Outcome Measures
Name Time Method Cohort A (Arms 1 and 2): Evaluate cretostimogene instillation methods At 11 and 24 weeks Evaluate cretostimogene genome and GM-CSF levels, treatment efficacy, and safety by 2 different methods of cretostimogene instillation in participants with pathologically confirmed CIS-containing high-risk NMIBC who are naïve to BCG treatment.
Cohort A (Arm 3): High-Grade Event-Free Survival at 12 months At 12 months Determine the proportion of participants with BCG-naive papillary-only high-grade NMIBC at baseline who are free from high-grade events at 12 months
Cohort A (Arms 1 and 2) and Cohort B (Arm 1) Duration of response 48 months Assess duration of response in participants with CIS with or without concomitant HG Ta/T1 disease at baseline
Cohort B (Arm 2) High-Grade Event-Free Survival at 12 months At 12 months Determine the proportion of participants with BCG-exposed papillary-only high-grade NMIBC at baseline who are free from high-grade events at 12 months
Cohort CX (Arm 1 and 2) Complete response rate At 11 and 24 weeks Determine the complete response rate at any time following treatment with cretostimogene and gemcitabine in participants with BCG-exposed or BCG-unresponsive CIS with or without concomitant high-grade Ta or T1 disease at baseline.
Trial Locations
- Locations (45)
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Arkansas Urology
🇺🇸Little Rock, Arkansas, United States
Michael G Oefelein, MD Clinical Trials
🇺🇸Bakersfield, California, United States
Genesis Research (Greater Los Angeles)
🇺🇸Torrance, California, United States
Advanced Urology
🇺🇸Los Angeles, California, United States
Urology Center of Southern California
🇺🇸Murrieta, California, United States
University of California, Irvine
🇺🇸Orange, California, United States
Univeristy of Southern California
🇺🇸San Diego, California, United States
Urology Associates, Lone Tree
🇺🇸Lone Tree, Colorado, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Advanced Urology Institute (Solaris)
🇺🇸Largo, Florida, United States
Advanced Urology Institute
🇺🇸Oxford, Florida, United States
Advanced Urogoloy Institute - Tallahassee (Solaris)
🇺🇸Tallahassee, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Associated Urological Specialists
🇺🇸Chicago Ridge, Illinois, United States
Uropartners
🇺🇸Glenview, Illinois, United States
Urology of Indiana - Carmel
🇺🇸Carmel, Indiana, United States
Urology of Indiana, LLC (US Urology Partners)
🇺🇸Greenwood, Indiana, United States
First Urology, PSC
🇺🇸Jeffersonville, Indiana, United States
Urologic Specialists of Northwest Indiana (Solaris)
🇺🇸Merrillville, Indiana, United States
Urology Center of Iowa Research
🇺🇸Clive, Iowa, United States
Wichita Urology Group
🇺🇸Wichita, Kansas, United States
Southern Urology (Urology America)
🇺🇸Lafayette, Louisiana, United States
Michigan Institute of Urology (Solaris)
🇺🇸Troy, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Specialty Clinical Research of St. Louis
🇺🇸Saint Louis, Missouri, United States
Integrated Medical Professionals, PLLC (Solaris)
🇺🇸New York, New York, United States
Associated Medical Professionals of NY, PLLC (US Urology Partners)
🇺🇸Syracuse, New York, United States
The Urology Group (Solaris)
🇺🇸Cincinnati, Ohio, United States
Central Ohio Urology Group (US Urology Partners)
🇺🇸Gahanna, Ohio, United States
Midlantic Urology (Solaris)
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Keystone Urology Specialists
🇺🇸Lancaster, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Charleston Area Medical Center
🇺🇸Charleston, South Carolina, United States
Carolina Urologic Research Center, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Lowcountry Urology (Solaris)
🇺🇸North Charleston, South Carolina, United States
The Conrad Pearson Clinic (Urology America)
🇺🇸Germantown, Tennessee, United States
Urology Associates, PC
🇺🇸Nashville, Tennessee, United States
Amarillo Urology Research
🇺🇸Amarillo, Texas, United States
UPNT Research Institute, LLC
🇺🇸Arlington, Texas, United States
Urology Austin, PLLC (Urology America)
🇺🇸Austin, Texas, United States
Urology Clinics of North Texas, PLLC
🇺🇸Dallas, Texas, United States
Urology San Antonio, PA dba USA Clinical Trials
🇺🇸San Antonio, Texas, United States
Urology of Virginia
🇺🇸Virginia Beach, Virginia, United States
Spokane Urology
🇺🇸Spokane, Washington, United States