Real-world outcomes of nadofaragene firadenovec in BCG-unresponsive non-muscle invasive bladder cancer.
Authors: Moyer Jacob A. , Durant Adri , Nguyen Mimi , Mi Lanyu , Zganjar Andrew , Lyon Timothy D. , Shah Paras H , Boorjian Stephen A. , Tyson Mark 
Published: February 2025

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Background:
Nadofaragene firadenovec is an FDA-approved gene therapy for Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) with promising clinical trial results. However, real-world post-marketing efficacy or safety data remain lacking. We evaluated complete response rates and safety in a multisite experience.
Methods:
Per IRB protocol, we analyzed patients treated with nadofaragene firadenovec for BCG-unresponsive NMIBC across three Mayo Clinic sites. Outcomes included complete response (CR), high-grade recurrence-free survival (HGRFS), cystectomy-free survival (CFS), overall survival (OS), and adverse events (AEs). CR and HGRFS were reported for patients with carcinoma in situ (CIS) and patients with Ta/T1 without CIS respectively. Failure to retain was defined as any medication loss, including leakage around the catheter or early voiding.
Results:
Between November 2023 and October 2024, 45 patients were treated with nadofaragene firadenovec for BCG-unresponsive NMIBC. Fifteen patients with follow-up less than 6 months and one patient with extensive metastatic disease identified one week after first instillation were excluded from efficacy analysis. Our efficacy-evaluable population of 29 patients with median follow-up of 8.2 months is summarized in the Table. CR/HGRFS at 3 and 6 months was 72% and 62% respectively. CFS was 94% and OS was 100% at 6 months. Three patients experienced disease progression during follow-up: one to T1, another to T2, and a third with metastases to the abdomen and lungs. A separate patient developed a metachronous upper tract urothelial carcinoma (pT2) without bladder recurrence. Bladder spasms (62%) and failure to retain (31%) were the most common AEs. Most AEs were low-grade, although four (9%) patients had grade 3 events (fatigue, fever, and dizziness). No grade 4-5 AEs were reported.
Conclusions:
Early real-world data demonstrates encouraging clinical complete response rates in patients with BCG-unresponsive NMIBC and a favorable safety profile. Further investigation with larger cohorts and longer follow-up is warranted.

Evaluable patients (N=29)
CIS cohort (N=15)
Ta/T1 only cohort (N=14)
Prior pembrolizumab (N=9)
Prior intravesical chemotherapy (N=16)

Age, years
72 (67-77)
74 (69-77)
71 (67-77)
69 (67-78)
73 (67-81)

Elixhauser Index
5 (4-6)
5 (4-7)
5 (4-6)
5 (3-5)
5 (3-6)

Prior BCG instillations
12 (10-14)
12 (12-15)
11 (8-13)
12 (12-12)
12 (11-13)

Prior intravesical chemotherapy among recipients
6 (6-11)
6 (6-10)
6 (6-11)
10 (7-12)
6 (6-11)

Prior pembrolizumab doses among recipients
7 (4-8)
8 (7-8)
4 (4-4)
7 (4-8)
8 (5-8)

Follow-up, months
8.2 (6.9-9.5)
7.6 (6.9-9.5)
8.5 (6.9-9.4)
9.1 (8.0-10.1)
8.6 (6.7-9.9)

3-month CR/HGRFS
72% [53-87]
73% [45-92]
71% [42-92]
67% [30-93]
56% [30-80]

6-month CR/HGRFS
62% [42-79]
67% [38-88]
57% [29-82]
44% [14-79]
44% [20-70]

Data are median (IQR) or % [95% CI].