Clinical use of nadofaragene firadenovec-vncg.

Non-muscle-invasive bladder cancer (NMIBC), which is restricted to the mucosa (stage Ta, carcinoma in situ (CIS)) or submucosa (stage T1), comprises 75% of bladder cancer diagnoses. Intravesical bacillus Calmette-Guérin (BCG) therapy is the standard-of-care initial treatment for high-risk NMIBC; however, a significant proportion of patients have BCG-unresponsive disease. While radical cystectomy is a definitive treatment in this setting, not all patients are willing or able to undergo this complex procedure associated with morbidity, mortality, and decreased quality of life. Bladder-preserving options for patients with BCG-unresponsive NMIBC represent an unmet need in this patient population. Nadofaragene firadenovec-vncg (Adstiladrin) is a nonreplicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors. The antitumor efficacy of nadofaragene firadenovec is driven by its local delivery of copies of the gene encoding for interferon alpha-2b (IFNα-2b) to urothelial cells. In the phase III CS-003 study, over half of participants with CIS exhibited a complete response by month 3 after instillation, with minimal serious adverse events. The favorable efficacy and safety profile, clinical utility, novel mechanism of action, and every 3-month dosing schedule give nadofaragene firadenovec a unique role in the treatment of high-risk BCG-unresponsive NMIBC. This review provides a practical approach to the effective clinical use of nadofaragene firadenovec regarding pre-instillation visit arrangements, storage, handling, instillation procedures, and post-instillation procedures. Implementation of these recommendations will ensure efficient real-world use of nadofaragene firadenovec and the development of useful training materials and relevant standard operating procedures to help support a clinic's treatment for patients with BCG-unresponsive NMIBC with CIS. Video Abstract https://vimeo.com/user17898099/review/953723559/e18af7ec43.
Competing Interests: B. R. K. served as a consultant/advisor and received funding from Photocure, Asieris Pharmaceuticals, Ferring Pharmaceuticals Inc., Illumina, Inc., and Abbott; and has ownership/investment interest in Astrin Biosciences and Styx Biotechnologies. N. D. S. served as a consultant and received funding from Astellas, Dendreon, Janssen, Bayer, Myriad, MDxHealth, Tolmar, Myovant, Pfizer, EMD Serono Inc, AstraZeneca, Merck, UroGen, Guardant, AbbVie, Amgen, Bristol Myers Squibb, Boston Scientific, Exact Imaging, Foundation Medicine, CG Oncology, Invitae, Propella, Sanofi, Pacific Edge, Alessa, Amgen, Arquer, Asieris, Clarity, Ferring Pharmaceuticals Inc., Lantheus, Lilly, Minomic, Nanogen, Novartis, Photocure, PlatformQ, Profound, Promaxo, Protara, Specialty Networks, Telix, FIZE Medical, Accord, Antev, BioProtect, Aura Biosciences, Palette Life, and Preview; and received funding from a leadership role in GenesisCare, Alessa, and Photocure. G. R. S. served as a consultant to Ferring Pharmaceuticals Inc.
(© The Author(s), 2024.)