Oncolytic and Immunotherapeutic CG0070 Adenovirus for High-risk Bacillus Calmette-Guerin Unresponsive Bladder Cancer

Abstract

Introduction To evaluate the response of patients with high-risk bacillus Calmette-Guerin (BCG)–unresponsive non-muscle invasive bladder cancer (NMIBC) who we treated with intravesical CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor (GM-CSF) containing an RB promoter. Methods 15 patients with residual high grade BCG-unresponsive CIS +/- Ta/T1/T2 bladder cancer received one or more 6-week instillations of intravesical CG0070 and were retrospectively reviewed. Overall response including the number, location, grade and stage of recurrences, were recorded. Side effects of intravesical instillation of CG0070 were also investigated. 11 of the 15 patients had at least 2.5 years of follow up both before and after treatment, permitting statistical chi-square analysis for the 2.5 year pre- and post-CG0070 periods. Results Of the 15 patients, 5 had Ta + Cis, 4 had T1 + CIS, 4 had CIS alone, and 2 had T2 + CIS prior to CG0070 instillation. Complete response of CIS was seen in 60% at 6 months, 47% at 12 months, and 40% at 24 months. Overall, 40% of patients remained tumor free and none progressed. For the 11 patients amenable to statistical analysis, 32 recurrences were noted within 2.5 years before therapy and 13 2.5 years after (p <0.01). 40% of patients experienced no adverse events as a result of treatment. Most common side effects were hematuria (33.3%), malaise/fatigue (33.3%), and urgency/frequency (26.7%). Discussion Treatment with intravesical CG0070 for high-risk BCG-unresponsive bladder cancer appears to be a promising salvage regimen worthy of further investigation.