AUA 2021: Anti-adenoviral Antibody Levels Predict Nadofaragene Firadenovec Response in BCG-unresponsive NMIBC- Results from a Phase 3 Trial 

( The bladder cancer non-invasive session at the American Urological Association, (AUA) included a presentation by Dr. Anirban Mitra discussing the impact of anti-adenoviral antibody levels for predicting nadofaragene firadenovec response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Nadofaragene firadenovec is a recombinant adenoviral vector-based intravesical therapeutic that delivers a copy of human IFNa2b gene to urothelial cells. The recent phase 3 trial in high-grade BCG-unresponsive NMIBC reported a 60% complete response rate in the efficacy population at 3 months, and this response was maintained in 51% of patients at 12 months.1 This analysis examined the value of anti-adenoviral antibody level as a predictor of therapeutic response in patients receiving nadofaragene firadenovec.

There were 157 BCG-unresponsive NMIBC patients treated in the single-arm, open-label phase 3 Instillidrin trial. For treatment, 75 mL of nadofaragene firadenovec (3 x 1011 vp/mL) was instilled intravesically for 1 hour once every 3 months for up to four doses, with additional dosing at the investigator's discretion. Serum antibody levels were assessed 1-24 hours pretreatment at baseline, and 3, 6, 9 and 12 months or at study-withdrawal visit. Assays were performed at laboratories certified per Clinical Laboratory Improvement Amendments (CLIA) standards. Fold change was calculated as the ratio of on-treatment to baseline antibody level. The final treatment response was assessed at 12 months or time of disease recurrence, whichever was earlier.

There were 91 (58%) patients in the treatment population that had evaluable antibody titers and were included in the analysis. Among those included, 57 (63%) patients had carcinoma in situ with or without Ta or T1 (CIS ± Ta/T1) disease. Overall, 47 (52%) patients were high-grade recurrence-free at month 12. On-treatment antibody titers for all patients were at or higher than baseline levels and baseline titers were not associated with response. On-treatment titers >800 were seen in 89% of responders and 59% of nonresponders (p=0.001).




The sensitivity of this test for detecting responders was 89% with a negative predictive value of 78%. On-treatment antibody fold change >8 from baseline was seen in 51% of responders and 27% of non-responders (p=0.02).




Elevated on-treatment antibody titers and fold change from baseline were noted in 47% of responders and 18% of non-responders (p=0.004). The specificity of the combined test for detecting responders was 82% with a positive predictive value of 73%.




Additionally, these findings were also corroborated in the CIS ± Ta/T1 sub-cohort of patients.

Dr. Mitra concluded his presentation of anti-adenoviral antibody levels predicting nadofaragene firadenovec response with the following take-home messages:

  • This secondary analysis of the prospective, multicenter phase 3 nadofaragene firadenovec trial in BCG-unresponsive NMIBC indicates a role for assaying baseline and on-treatment antibody titers
  • A combination of antibody titer and fold-change levels can potentially predict response to this novel therapeutic in a patient population with urgent unmet clinical need
  • BCG-unresponsive NMIBC patients with non-durable response may be candidates for other combinatorial therapies


Presented by: Anirban P. Mitra, MD, Ph.D., UT MD Anderson Cancer Center, MD Anderson Cancer Center, Houston, TX

Co-Authors: Vikram M Narayan, Stephen A Boorjian, Mehrdad Alemozaffar, Badrinath R Konety, Neal D Shore, Leonard G Gomella, Ashish M Kamat, Trinity J Bivalacqua, Jeffrey S Montgomery, Seth P Lerner, Joseph E Busby, Michael Poch, Paul L Crispen, Gary D Steinberg, Anne K Schuckman, Tracy M Downs, Robert S Svatek, Joseph Mashni Jr, Brian R Lane, Thomas J Guzzo, Gennady Bratslavsky, Lawrence I Karsh, Michael E Woods, Gordon Brown, Daniel Canter, Adam Luchey, Yair Lotan, Tracey Krupski, Brant A Inman, Michael B Williams, Michael S Cookson, Kirk A Keegan, Gerald L Andriole Jr, Alexander I Sankin, Alan Boyd, Michael A O'Donnell, Mindy Yang, David Sawutz, Richard Philipson, Seppo Ylä-Herttuala, Nigel R Parker, Colin P N Dinney


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 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.


  1. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: A single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2020 Nov 27:S1470-2045(20)30540-4.


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