Abstract IA21: Intravesical gene therapy for NMIBC

BCG is our most effective therapy for treating NMIBC, but over time, most patients will eventually recur. Alternative therapies to avoid cystectomy are needed as to date, only valrubicin, with a CR approaching 10% at 12 months in BCG-refractory CIS, has been FDA approved. Significant unmet need thus remains for an effective second-line therapy for patients facing cystectomy. The elucidation of a pathway for registration of new agents for BCG-unresponsive NMIBC has drawn the attention of pharma, and a variety of new approaches are under evaluation. Gene therapy is a promising approach for the management of BCG-unresponsive NMIBC. Effective gene transfer across the urothelium has been accomplished, and several agents are being evaluated in ongoing clinical trials. Coldgenesys reported a 47% CR at 6 months for BCG-unresponsive NMIBC using a replication-competent oncolytic adenovirus. The SUO CTC reported a 35% RFS at 12 months for patients treated with rAd-IFNα2b/Syn3 gene therapy in a phase II trial. The RFS for patients with papillary disease was 50% and the CR for patients with CIS was 30%. The SUO-CTC have recently completed recruitment for the phase III trial and further preclinical work has progressed to elucidate rAd-IFN/Syn3 treatment efficacy via predictive efficacy biomarkers for patient selection, vectors that might improve transduction efficiency and the design of novel therapeutic combination strategies to take advantage of rAd-IFN's immunologic activity.

Citation Format: Sharada Mokkapati, Jon Duplisea, Michael Metcalfe, Amy Lim, Vikram Narayan, Devin Plote, Debashish Sundi, James E. Furguson III, Nigel R. Parker, Seppo Yla-Herttuala, David McConkey, Kimberly S. Shluns, Colin P.N. Dinney. Intravesical gene therapy for NMIBC [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA21.