Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin

An open-label trial designed to evaluate Cretostimogene + DDM in patients with NMIBC who have failed prior BCG therapy. Single treatment arm that enrolled patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease.

Inclusion criteria

In order to be eligible for participation in this trial, the patient must:

• Be ≥18 years of age on day of signing informed consent.

• Patients must have pathologically confirmed BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without concomitant Ta/T1 papillary disease.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have all Ta and/or T1 disease resected and all CIS resected or fulgurated, as feasible, prior to study treatment.
• Demonstrate adequate organ function.
• Patients must be willing to comply with study mandated cystoscopies, urine cytology, urograms, biopsies, and other procedures (including TURBT or other resection for all Ta/T1 disease) for the duration of the study. Patients who withdraw consent for these procedures will be withdrawn from the trial.
• Ineligible to receive radical cystectomy or refusal of radical cystectomy according to Investigator assessment.

Exclusion criteria

• Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
• History of urothelial carcinoma in the upper genitourinary tract (kidney, renal collecting system, ureter) or in the prostatic urethra, including urethral CIS, within 24 months prior to enrollment.
• Has received systemic anti-cancer therapy, including investigational agents.
• Has had prior systemic treatment (with the exception of checkpoint inhibitor therapy), radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
• Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure.
• Cannot tolerate study-related biopsies, IVE administration, or 1-hour bladder hold of Cretostimogene.