Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC
Purpose
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.
Condition
- High-Risk Non-Muscle-Invasive Bladder Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Experimental: Cohort A, Arm 1 |
Cretostimogene (1 x 1012 vp) will be administered intravesically via the current instillation method |
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Experimental Experimental: Cohort A, Arm 2 |
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. |
|
|
Experimental Experimental: Cohort A, Arm 3 |
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. |
|
|
Experimental Experimental: Cohort B, Arm 1 |
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. |
|
|
Experimental Experimental: Cohort B, Arm 2 |
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method. |
|
|
Experimental Experimental: Cohort CX, Arm 1 |
At all treatment visits cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method followed by gemcitabine instilled intravesically |
|
|
Experimental Experimental: Cohort CX, Arm 2 |
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 |
|
Recruiting Locations
Little Rock, Arkansas 72211
Bakersfield, California 93301
Michael G Oefelein, MD
661-310-1063
Los Alamitos, California 90720
Murrieta, California 92563
San Diego, California 92123
Torrance, California 90503
Lone Tree, Colorado 80124
Largo, Florida 33771
Oxford, Florida 34484
Tallahassee, Florida 32308
Chicago Ridge, Illinois 60415
Carmel, Indiana 46032
Greenwood, Indiana 46143
Jeffersonville, Indiana 47130
Merrillville, Indiana 46410
Clive, Iowa 50325
Wichita, Kansas 67226
Lafayette, Louisiana 70508
Troy, Michigan 48084
Saint Louis, Missouri 63141
New York, New York 10016
Syracuse, New York 13210
Cincinnati, Ohio 45212
Gahanna, Ohio 43230
Bala-Cynwyd, Pennsylvania 19004
Lancaster, Pennsylvania 17604
Philadelphia, Pennsylvania 19104
Charleston, South Carolina 25304
Myrtle Beach, South Carolina 229572
North Charleston, South Carolina 29406
Germantown, Tennessee 38138
Nashville, Tennessee 37209
Amarillo, Texas 79106
Arlington, Texas 76017
Austin, Texas 78745
Dallas, Texas 75231
San Antonio, Texas 78229
Virginia Beach, Virginia 23462
Spokane, Washington 99202
More Details
- NCT ID
- NCT06567743
- Status
- Recruiting
- Sponsor
- CG Oncology, Inc.
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.