Abstract
EFFICACY OF INTRAVESICAL NADOFARAGENE FIRADENOVEC FOR PATIENTS WITH BCG-UNRESPONSIVE CARCINOMA IN SITU OF THE BLADDER: 36-MONTH FOLLOW-UP FROM A PHASE 3 TRIAL
Urologic oncology, Vol.42(Supplement), pp.S70-S70
03/2024
DOI: 10.1016/j.urolonc.2024.01.201
Abstract
Patients with Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) are at significant risk for recurrence and progression and there is an unmet need for local, effective, bladder-preserving treatment options. Nadofaragene firadenovec, a non-replicating recombinant adenovirus vector-based gene therapy that delivers a copy of the human interferon alfa-2b gene into the bladder epithelium, is approved by the FDA for treatment of adult patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (±Ta/T1). The Phase 3 study of nadofaragene firadenovec met its primary endpoint;;53.4% of patients with CIS±Ta/T1 achieved;complete response (CR) at three months. The 24-month follow-up results showed that nadofaragene firadenovec was well tolerated, and 36.4% of the patients with CIS±Ta/T1 who achieved a CR remained high-grade recurrence free (HGRF) at 24 months. Herein, we report 36-month follow-up results from the Phase 3 study for the CIS±Ta/T1 cohort.
The open-label Phase 3 study enrolled 107 patients with BCG-unresponsive NMIBC with CIS±Ta/T1 (NCT02773849). The efficacy analysis for this cohort included 103 patients who met the protocol definition of BCG-unresponsive NMIBC. Patients received 75 mL of nadofaragene firadenovec (3×1011 viral particles/mL) once every 3 months for up to 4 doses. The protocol mandated a 5-site biopsy (dome, trigone, right and left lateral walls, posterior wall) at 12 months and patients who were HGRF were offered continued treatment once every 3 months at the investigator's discretion. Assessments beyond 24 months were performed in accordance with usual clinical practice. The study is ongoing, with a planned 5-year treatment and monitoring phase; the follow-up results reported here are based on the 36-month interim data for the CIS±Ta/T1 cohort.
Mean (standard deviation) duration of follow-up for the entire cohort was 42.1 (12.6) months*, with a total of 13/107 (12.1%) patients having received 36 months of treatment.At 36 months, 14/55 (25.5%) patients who had achieved a CR at 3 months remained HGRF. For these patients, the Kaplan–Meier (KM)-estimated probability of duration of CR for at least 12, 24 and 36 months was 46.5%, 36.6% and 34.2%, respectively (Figure).In the overall CIS±Ta/T1 cohort (N=103), the KM-estimated median (95% confidence interval [CI]) duration of HGRF survival was 6.0 (3.4, 8.3) months, and probability;(95% CI) of HGRF survival for at least 12 months was 30.1% (21.5, 39.2). Two patients (1.9%) discontinued due to adverse events, while four (3.9%) experienced progression to muscle-invasive disease. The KM-estimated cystectomy-free survival (95% CI) at 36 months was 53.8% (43.3, 63.1), and the three-year overall survival was 90.4% (82.3, 94.9).
Intravesical nadofaragene firadenovec, administered once every three months, demonstrated a sustained durability of response in patients with BCG-unresponsive CIS±Ta/T1 papillary disease. Nadofaragene firadenovec represents a novel treatment option for BCG-unresponsive NMIBC with a favorable benefit-to-risk ratio.*All patients had passed 36 months at data cutoff on 09 September 2021.Figure. Kaplan–Meier estimated durability of complete response in patients with CIS±Ta/T1 papillary disease.
Details
- Title: Subtitle
- EFFICACY OF INTRAVESICAL NADOFARAGENE FIRADENOVEC FOR PATIENTS WITH BCG-UNRESPONSIVE CARCINOMA IN SITU OF THE BLADDER: 36-MONTH FOLLOW-UP FROM A PHASE 3 TRIAL
- Creators
- Stephen A. Boorjian - Mayo ClinicVikram M. Narayan - Emory University School of MedicineViraj A. Master - Emory University School of MedicineBadrinath R. Konety - University of MinnesotaNeal D. Shore - Carolina Urologic Research CenterAshish M. Kamat - The University of Texas MD Anderson Cancer CenterColin P.N. Dinney - The University of Texas MD Anderson Cancer CenterTrinity J. Bivalacqua - Johns Hopkins University School of MedicineMax R. Kates - Johns Hopkins University School of MedicineJeffrey S. Montgomery - University of MichiganSeth P. Lerner - Baylor College of MedicinePaul L. Crispen - University of FloridaGary D. Steinberg - Rush UniversityPiyush K. Agarwal - University of ChicagoAnne K. Schuckman - University of Southern CaliforniaRobert S. Svatek - The University of Texas Health Science Center at San AntonioBrian R. Lane - Michigan State UniversityLawrence I. Karsh - The Urology Center of ColoradoMarc A. Bjurlin - University of North Carolina at Chapel HillYair Lotan - The University of Texas Southwestern Medical CenterGordon A. Brown - New Jersey UrologyBrant A. Inman - Duke University School of MedicineMichael B. Williams - Urology of VirginiaMichael S. Cookson - University of Oklahoma Health Sciences CenterSam S. Chang - Vanderbilt UniversityEric H. Kim - Barnes-Jewish HospitalAlexander I. Sankin - Montefiore Medical CenterMichael A. O'Donnell - University of IowaJørn S. Jakobsen - Ferring PharmaceuticalsKristian Juul - Ferring Pharmaceuticals
- Resource Type
- Abstract
- Publication Details
- Urologic oncology, Vol.42(Supplement), pp.S70-S70
- DOI
- 10.1016/j.urolonc.2024.01.201
- ISSN
- 1078-1439
- eISSN
- 1873-2496
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/2024
- Academic Unit
- Urology
- Record Identifier
- 9984573949402771
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