(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Trials in Progress Poster Session B: Urothelial Carcinoma. Dr. Sia Daneshmand presented trial in progress poster 891: ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy—A randomized, open-label, phase 2 study.
Dr. Daneshmand began his presentation by highlighting that nadofaragene firadenovec-vncg is a nonreplicating, nonintegrating adenoviral vector-based gene therapy approved by the FDA for the treatment of high-risk, BCG-unresponsive NMIBC with CIS, with or without papillary tumors. The therapy’s efficacy was demonstrated in the pivotal open-label phase 3 trial (NCT02773849), which showed that at 60 months, nadofaragene firadenovec-vncg enabled bladder preservation in 49% of patients.1 Additionally, 53.4% of participants with high-risk, BCG-unresponsive NMIBC with CIS ± Ta/T1 achieved a complete response within 3 months following a single instillation of the therapy.2
However, despite encouraging results with FDA-approved therapies for patients with BCG-unresponsive NMIBC, there is still an unmet need to further improve CR rates and durability. Dr. Daneshmand discussed that ABLE-22 will evaluate the safety and efficacy of intravesical instillation of nadofaragene firadenovec and its reinduction
alone or in combination with chemotherapy or immunotherapy
in participants with high-risk BCG-unresponsive NMIBC.
The primary objective of the study is to evaluate the efficacy of intravesical instillation of nadofaragene firadenovec, administered every 3 months, either alone or in combination with chemotherapy (gemcitabine and docetaxel) or immunotherapy (pembrolizumab), in participants with high-risk BCG-unresponsive NMIBC with CIS ± concomitant high-grade Ta/T1. Notably, participants with persistent NMIBC at month 3 will be offered reinduction therapy.
Secondary objectives and endpointsKey secondary endpoints include:
- Durability of complete response
- Incidence of muscle-invasive progression
- Cystectomy-free survival
- Pathologic staging
- Overall survival
- Safety.
Exploratory endpoints will assess changes in the expression of potential biomarkers in blood and urine, from screening to the end of treatment or at the time of withdrawal.
Dr. Daneshmand wrapped up his presentation by sharing the ABLE-22 study design:
Presented by: Sia Daneshmand, MD, Urologic Oncologist, Professor of Urology and Medicine at the University of Southern California (USC) in Los Angeles, CA.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
References:
- Narayan VM, 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, Mashni J Jr, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Inman BA, Williams MB, Cookson MS, Chang SS, Sankin AI, O'Donnell MA, Sawutz D, Philipson R, Parker NR, Yla-Herttuala S, Rehm D, Jakobsen JS, Juul K, Dinney CPN. Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial. J Urol. 2024 Jul;212(1):74-86. doi: 10.1097/JU.0000000000004020. Epub 2024 May 5. PMID: 38704840.
- Narayan VM, Meeks JJ, Jakobsen JS, Shore ND, Sant GR, Konety BR. Mechanism of action of nadofaragene firadenovec-vncg. Front Oncol. 2024 Mar 15;14:1359725. doi: 10.3389/fonc.2024.1359725. PMID: 38559556; PMCID: PMC10979480.