Non-replicating adenovirus vectors are widely used due to their advantages as a gene delivery vehicle. However, a crucial concern is that adenovirus vector-mediated transduction is suppressed in individuals with pre-existing anti-adenovirus neutralizing antibodies. The most commonly used recombinant adenovirus is based on adenovirus type 5 (Ad5). Most adults have pre-existing antibodies to adenovirus as a result of previous environmental exposure. This analysis focused on the correlation of the anti-adenoviral antibody levels to response rate, a secondary objective of the trial.
For this study, blood samples for anti-adenoviral antibody level assessments were collected between 24 and 1-hour pre-dose on days 1 and 3, 6, 9, and 12 months or at a withdrawal-from-treatment study visit. A patient was considered to have a positive immunogenic response if a post-baseline anti-adenoviral antibodies titration demonstrated a >2-fold dilution increase from baseline. This analysis was based on the data cut-off at 15 months.
Of the 151 patients included in the efficacy analysis, 129 had anti-adenoviral antibody titer results and were included in this analysis. 
Among the 55 patients who achieved a complete response in the CIS ± Ta/T1 cohort, significantly more patients had a positive post-baseline immunogenic response (43 vs 8; p= 0.0033). This was similarly observed in the high-grade Ta/T1 cohort where among the 34 patients who remained free of high-grade recurrence at 3 months, significantly more patients had a positive post-baseline immunogenic response (30 vs 4; p= 0.0003):
At 15 months of follow-up, the same trends were noted among patients who remained free of high-grade recurrence, with 19 vs 3 (p=0.1032) in the CIS ± Ta/T1 cohort and 17 vs 2 (p=0.08) patients in the high-grade Ta/T1 cohort who had a post-baseline immunogenic response.
Dr. Narayan concluded his presentation with the following take-home messages:
- Nadofaragene firadenovec instilled intravesically once every 3 months achieves durable complete responses in patients with high-grade, BCG-unresponsive NMIBC
- Titer data suggest that significant anti-adenovirus antibody response is associated with treatment response and may be used to identify responders
- Community exposure to adenoviruses does not appear to preclude the efficacy of the agent
- Nadofaragene firadenovec demonstrates promising efficacy and is a potential novel therapeutic option in a patient population with an urgent unmet medical need
Presented By: Vikram Narayan, MD, Emory University School of Medicine, Dept. of Urology, Atlanta, GA
Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
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