High-Risk Non-Muscle-Invasive Bladder Cancer
Conditions
Keywords
Bladder Cancer
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.
Interventions
Respective Cohort
Sponsors
CG Oncology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada, United States
Contacts
CONTACTRebecca Tregunna, MD
CONTACTPat Keegan, MD
STUDY_DIRECTORVijay Kasturi, MD
CG Oncology
Outcome results
None listed