Clinical trial NCT06567743: Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC
Official title: 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 (NMIBC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: High-Risk Non-Muscle-Invasive Bladder Cancer
Keywords: Bladder Cancer
Lead sponsor: CG Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-23
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Cohort A Key Inclusion Criteria:

* 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

Primary outcomes:
measure: Cohort A (Arm 1 and 2): Complete response rate
timeFrame: At 11 and 24 weeks
measure: Cohort A (Arm 3): High- Grade Event-Free Survival
timeFrame: 48 months
measure: Cohort B (Arm 1): Complete response rate
timeFrame: At 11 and 24 weeks
measure: Cohort B (Arm 2): High-Grade Event-Free Survival
timeFrame: 48 months
measure: Cohort CX (Arms 1 and 2): High-Grade Event-Free Survival
timeFrame: 48 months
measure: Cohort CX (Arms 1 and 2): Safety
timeFrame: 48 months
Secondary outcomes:
measure: Cohort A (Arms 1 and 2): Evaluate cretostimogene instillation methods
timeFrame: At 11 and 24 weeks
measure: Cohort A (Arm 3): High-Grade Event-Free Survival at 12 months
timeFrame: At 12 months
measure: Cohort A (Arms 1 and 2) and Cohort B (Arm 1) Duration of response
timeFrame: 48 months
measure: Cohort B (Arm 2) High-Grade Event-Free Survival at 12 months
timeFrame: At 12 months
measure: Cohort CX (Arm 1 and 2) Complete response rate
timeFrame: At 11 and 24 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Urology Specialty
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Bakersfield
country: United States
facility: Michael G Oefelein, MD Clinical Trials
state: California
city: Los Alamitos
country: United States
facility: Genesis Research (Greater Los Angeles)
state: California
city: Los Angeles
country: United States
facility: Advanced Urology
state: California
city: Murrieta
country: United States
facility: Urology Center of Southern California
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: San Diego
country: United States
facility: Univeristy of Southern California
state: California
city: Torrance
country: United States
facility: Genesis Research (Greater Los Angeles)
state: California
city: Lakewood
country: United States
facility: Colorado Urology
state: Colorado
city: Lone Tree
country: United States
facility: Urology Associates, Lone Tree
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Largo
country: United States
facility: Advanced Urology Institute (Solaris)
state: Florida
city: Oxford
country: United States
facility: Advanced Urology Institute
state: Florida
city: Tallahassee
country: United States
facility: Advanced Urogoloy Institute - Tallahassee (Solaris)
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago Ridge
country: United States
facility: Associated Urological Specialists
state: Illinois
city: Glenview
country: United States
facility: Uropartners
state: Illinois
city: Carmel
country: United States
facility: Urology of Indiana - Carmel
state: Indiana
city: Greenwood
country: United States
facility: Urology of Indiana, LLC (US Urology Partners)
state: Indiana
city: Jeffersonville
country: United States
facility: First Urology, PSC
state: Indiana
city: Merrillville
country: United States
facility: Urologic Specialists of Northwest Indiana (Solaris)
state: Indiana
city: Clive
country: United States
facility: Urology Center of Iowa Research
state: Iowa
city: Wichita
country: United States
facility: Wichita Urology Group
state: Kansas
city: Lafayette
country: United States
facility: Southern Urology (Urology America)
state: Louisiana
city: Hanover
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Troy
country: United States
facility: Michigan Institute of Urology (Solaris)
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Specialty Clinical Research of St. Louis
state: Missouri
city: New York
country: United States
facility: Integrated Medical Professionals, PLLC (Solaris)
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY, PLLC (US Urology Partners)
state: New York
city: Cincinnati
country: United States
facility: The Urology Group (Solaris)
state: Ohio
city: Gahanna
country: United States
facility: Central Ohio Urology Group (US Urology Partners)
state: Ohio
city: Bala-Cynwyd
country: United States
facility: Midlantic Urology (Solaris)
state: Pennsylvania
city: Lancaster
country: United States
facility: Keystone Urology Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: North Charleston
country: United States
facility: Lowcountry Urology (Solaris)
state: South Carolina
city: Germantown
country: United States
facility: The Conrad Pearson Clinic (Urology America)
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Urology Research
state: Texas
city: Arlington
country: United States
facility: UPNT Research Institute, LLC
state: Texas
city: Austin
country: United States
facility: Urology Austin, PLLC (Urology America)
state: Texas
city: Dallas
country: United States
facility: Urology Clinics of North Texas, PLLC
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio, PA dba USA Clinical Trials
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Spokane
country: United States
facility: Spokane Urology
state: Washington
Study officials:
affiliation: CG Oncology
name: Pat Keegan
role: STUDY_DIRECTOR
References: