Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non–muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial

Anirban P. Mitra, Vikram M. Narayan, Sharada Mokkapati, Tanner Miest, 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, J. Erik Busby, Michael Poch, Paul L. Crispen, Gary D. Steinberg, Anne K. Schuckman, Tracy M. Downs, Robert S. SvatekJoseph Mashni, Brian R. Lane, Thomas J. Guzzo, Gennady Bratslavsky, Lawrence I. Karsh, Michael E. Woods, Gordon A. Brown, Daniel Canter, Adam Luchey, Yair Lotan, Tracey Krupski, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Kirk A. Keegan, Gerald L. Andriole, Alexander I. Sankin, Alan Boyd, Michael A. O'Donnell, Richard Philipson, Seppo Ylä-Herttuala, David Sawutz, Nigel R. Parker, David J. McConkey, Colin P.N. Dinney

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. Patient summary: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer. Prospective assessment of serum anti–human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalEuropean Urology
Volume81
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • Antiadenovirus antibody
  • Bladder cancer
  • Companion biomarker
  • Gene therapy
  • Treatment efficacy

ASJC Scopus subject areas

  • Urology

Fingerprint

Dive into the research topics of 'Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non–muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial'. Together they form a unique fingerprint.

Cite this