(UroToday.com) The 2025 GU ASCO annual meeting featured a urothelial carcinoma trials in progress session and a presentation by Dr. Neal Shore discussing ABLE-32, a randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer. There is currently no FDA-approved treatment for intermediate-risk non–muscle-invasive bladder cancer, defined by the AUA as recurrence of low-grade Ta within 1 year, solitary low-grade Ta >3 cm, multifocal low-grade Ta, high-grade Ta (≤3 cm), and/or low-grade T1 (~50% risk of recurrence). Nadofaragene firadenovec-vncg is the first FDA-approved intravesical non-replicating gene therapy for the treatment of adult patients with high-risk BCG-unresponsive non–muscle-invasive bladder cancer with CIS with or without papillary tumors. Nadofaragene firadenovec is a non-replicating and non-integrating adenoviral vector-based gene therapy that delivers the human IFNa2b gene to urothelial cells, and Syn3, to enhance viral transduction of the urothelium:
In a nonrandomized, multicenter, open-label, repeat-dose, phase 3 study, 53.4% of participants (55/103) with CIS ± high-grade Ta/T1 achieved complete response 3 months after the first instillation [1]. Nadofaragene firadenovec was well tolerated, with no grade 4/5 study drug-related adverse events. Because maintenance treatment with nadofaragene firadenovec following tumor resection may improve clinical outcomes in patients with intermediate-risk non–muscle-invasive bladder cancer, the ABLE-32 open-label randomized study is being conducted to evaluate the efficacy of nadofaragene firadenovec administered every 3 months versus observation in participants with intermediate-risk non–muscle-invasive bladder cancer.
This phase 3 study includes approximately 100 global sites with 454 anticipated participants. Adults diagnosed with new or recurrent intermediate-risk non–muscle-invasive bladder cancer and having undergone TURBT within 60 days prior to randomization are eligible. Participants will be randomly assigned 1:1 to receive nadofaragene firadenovec or continue observation. The nadofaragene firadenovec group will receive quarterly doses unless disease recurs or progresses. The observation group will be followed quarterly and may receive nadofaragene firadenovec if intermediate-risk non–muscle-invasive bladder cancer recurs within 24 months. All participants will be evaluated for recurrence and progression using cytology, cystoscopy, and for-cause biopsy for up to 5 years:
The primary endpoint is recurrence free survival, from randomization to first documented recurrence, progression, or death. Secondary endpoints include recurrence free survival at 12 and 24 months and safety. Exploratory endpoints include effect on potential biomarkers and health-related quality of life. Participants are expected to be observed through 60 months. Final results from ABLE-32 are expected in 2031:
Presented by: Neal D. Shore, MD, FACS, Carolina Urologic Research Center, Myrtle Beach, SC
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md 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.
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