ASCO GU 2020: Safety and Efficacy of Intravesical Nadofaragene Firadenovec for patients with High-Grade, BCG Unresponsive Nonmuscle Invasive Bladder Cancer - Phase 3 Trial Results

San Francisco, California ( Intravesical BCG is a mainstay treatment for non-muscle invasive bladder cancer (NMIBC). However, a subset of patients undergoing BCG therapy will have unresponsive disease and are at significant risk of disease recurrence and progression to muscle-invasive disease. This clinical scenario remains challenging, as while cystectomy may be indicated, this option is may not be preferred by the patient or the morbidity of surgery may be prohibitive. There is a clear need for bladder-preserving therapies for BCG-unresponsive NMIBC. In the Rapid Abstract Session for Urothelial Carcinoma, Stephen Boorjian, MD of the Mayo Clinic presented results of a multicenter, open-label Phase III study of nadofaragene firadenovec in this patient population.

Nadofaragene firadenovec is novel intravesical gene-mediated therapy that delivers the IFNa2b gene, resulting in increased IFNa2b expression. Dr Boorjian explained that in a previous Phase II study, durable responses were observed with a 35% rate of high-grade recurrence free survival. In this Phase III study, Nadofaragene was administed once every 3 months for up to 4 doses in the first 12 months, with further doses at discretion. The primary endpoint was complete response (CR) at any time in patients with carcinoma in situ (CIS). 

A total of 157 patients with NMIBC, defined as CIS with or without T1/T1 or Ta/T1 alone, comprised the safety population with 151 in the efficacy population. Dr Boorjian highlighted key efficacy results: among the 103 patients with CIS, there was a 53.4% CR rate all of which occurred within 3 months of therapy. Of the patients who achieved CIS who achieved a CR, 45.5% maintained this CR at the 12 month mark – confirmed on biopsy. 

Most treatment-related adverse events were irritative urinary symptoms including bladder spasm, urinary urgency, hematuria. There were only 3 (1.9%) treatment-related adverse events prompting therapy discontinuation.

In summary, nadofargene firadenovec was associated with a promisingly high CR rate in patients with BCG-unresponsive CIS with a tolerable safety profile and evidence of durable response to 1 year. Clinically, this therapy is a promising alternative to surgery for this patient population.

Presented by: Stephen A Boorjian, MD, Mayo Clinic, Rochester, MN

Written by: Anis Hamid, MBBS, Medical Oncology Research Fellow at Dana-Farber Cancer Institute and Medical Oncologist, PhD candidate, University of Melbourne, Australia (Twitter: @anis_a_hamid) at the 2020 ASCO Genitourinary Cancers Symposium (#ASCO #GU20), February 13thto 15th, 2020, San Francisco, CA

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