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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.

Publication ,  Journal Article
Mitra, AP; Narayan, VM; Mokkapati, S; Miest, T; Boorjian, SA; Alemozaffar, M; Konety, BR; Shore, ND; Gomella, LG; Kamat, AM; Bivalacqua, TJ ...
Published in: European urology
March 2022

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.

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Published In

European urology

DOI

EISSN

1873-7560

ISSN

0302-2838

Publication Date

March 2022

Volume

81

Issue

3

Start / End Page

223 / 228

Related Subject Headings

  • Urology & Nephrology
  • Urinary Bladder Neoplasms
  • Prospective Studies
  • Neoplasm Recurrence, Local
  • Neoplasm Invasiveness
  • Male
  • Humans
  • Female
  • BCG Vaccine
  • Antineoplastic Agents
 

Citation

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Mitra, A. P., Narayan, V. M., Mokkapati, S., Miest, T., Boorjian, S. A., Alemozaffar, M., … Dinney, C. P. N. (2022). 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. European Urology, 81(3), 223–228. https://doi.org/10.1016/j.eururo.2021.12.009
Mitra, Anirban P., Vikram M. Narayan, Sharada Mokkapati, Tanner Miest, Stephen A. Boorjian, Mehrdad Alemozaffar, Badrinath R. Konety, et al. “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.European Urology 81, no. 3 (March 2022): 223–28. https://doi.org/10.1016/j.eururo.2021.12.009.
Mitra, Anirban P., et al. “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.European Urology, vol. 81, no. 3, Mar. 2022, pp. 223–28. Epmc, doi:10.1016/j.eururo.2021.12.009.
Mitra AP, Narayan VM, Mokkapati S, Miest T, Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Svatek RS, Mashni J, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown GA, Canter D, Luchey A, Lotan Y, Krupski T, Inman BA, Williams MB, Cookson MS, Keegan KA, Andriole GL, Sankin AI, Boyd A, O’Donnell MA, Philipson R, Ylä-Herttuala S, Sawutz D, Parker NR, McConkey DJ, Dinney CPN. 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. European urology. 2022 Mar;81(3):223–228.
Journal cover image

Published In

European urology

DOI

EISSN

1873-7560

ISSN

0302-2838

Publication Date

March 2022

Volume

81

Issue

3

Start / End Page

223 / 228

Related Subject Headings

  • Urology & Nephrology
  • Urinary Bladder Neoplasms
  • Prospective Studies
  • Neoplasm Recurrence, Local
  • Neoplasm Invasiveness
  • Male
  • Humans
  • Female
  • BCG Vaccine
  • Antineoplastic Agents