Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC

CG Oncology

Status and phase: Enrolling; Phase 2

Conditions: High-Risk Non-Muscle-Invasive Bladder Cancer

Treatments: Drug: Cretostimogene Grenadenorepvec

Study type: Interventional

Funder types: Industry

Identifiers

NCT06567743

CORE-008

Details and patient eligibility

About

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.

Full 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.

Enrollment: 325 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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325 participants in 7 patient groups

Experimental: Cohort A, Arm 1

Experimental group

Description:

Cretostimogene (1 x 1012 vp) will be administered intravesically via the current instillation method

Treatment:

Drug: Cretostimogene Grenadenorepvec

Experimental: Cohort A, Arm 2

Experimental group

Description:

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Treatment:

Drug: Cretostimogene Grenadenorepvec

Experimental: Cohort A, Arm 3

Experimental group

Description:

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Treatment:

Drug: Cretostimogene Grenadenorepvec

Experimental: Cohort B, Arm 1

Experimental group

Description:

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Treatment:

Drug: Cretostimogene Grenadenorepvec

Experimental: Cohort B, Arm 2

Experimental group

Description:

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Treatment:

Drug: Cretostimogene Grenadenorepvec

Experimental: Cohort CX, Arm 1

Experimental group

Description:

At all treatment visits cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method followed by gemcitabine instilled intravesically

Treatment:

Drug: Cretostimogene Grenadenorepvec

Experimental: Cohort CX, Arm 2

Experimental group

Description:

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

Treatment:

Drug: Cretostimogene Grenadenorepvec