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 Sex
- 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. |
|
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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
Gilbert, Arizona 85234
Little Rock, Arkansas 72205
Little Rock, Arkansas 72211
Bakersfield, California 93301
Michael G Oefelein, MD
661-310-1063
Los Alamitos, California 90720
Murrieta, California 92563
Sacramento, California 95817
San Diego, California 91223
San Diego, California 92123
Torrance, California 90503
Lone Tree, Colorado 80124
Gainesville, Florida 32611
Largo, Florida 33771
Oxford, Florida 34484
Chicago Ridge, Illinois 60415
Lisle, Illinois 60532
Carmel, Indiana 46032
Greenwood, Indiana 46143
Jeffersonville, Indiana 47130
Merrillville, Indiana 46410
Clive, Iowa 50325
Wichita, Kansas 67226
Lafayette, Louisiana 70508
Annapolis, Maryland 21401
Hanover, Maryland 21076
Boston, Massachusetts 02115
Royal Oak, Michigan 48073
Troy, Michigan 48084
Woodbury, Minnesota 55123
St Louis, Missouri 63141
Omaha, Nebraska 68114
Hackensack, New Jersey 07601
New York, New York 10016
Rochester, New York 14620
Syracuse, New York 13210
The Bronx, New York 10461
Chapel Hill, North Carolina 27599
Mary Westerman, MD
Charlotte, North Carolina 28204
Raleigh, North Carolina 27612
Cincinnati, Ohio 45212
Cincinnati, Ohio 45267
Gahanna, Ohio 43230
Portland, Oregon 97239
Portland, Oregon 97239
Nicholas Chakiryan, MD
Springfield, Oregon 97447
Bala-Cynwyd, Pennsylvania 19004
Hershey, Pennsylvania 17033
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
Arlington, Texas 76017
Austin, Texas 78745
Dallas, Texas 75231
Dallas, Texas 75390
Catherine Rodriguez
214-645-8787
San Antonio, Texas 78229
Alexandria, Virginia 22311
Virginia Beach, Virginia 23462
Spokane, Washington 99202
More Details
- 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.