Intravesical nadofaragene firadenovec sustains a therapeutic response over 24 months in patients with nonmuscle-invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guérin (BCG), including in those with carcinoma in situ (CIS) or high-grade Ta/T1 alone. Investigators presented follow-up data from their original phase 3 trial at the AUA2021 Virtual Experience.
“Nadofaragene firadenovec represents a potential novel treatment option for patients with high-grade BCG-unresponsive NMIBC that advances the current treatment and demonstrates sustained durability of response,” investigators concluded in 2 poster presentations.
The novel gene therapy greatly increases expression of interferon alfa in bladder epithelial cells and has proven more effective than instilling the cytokine itself, the University of Texas team explained.
In the original phase 3 trial published in The Lancet Oncology (NCT02773849), 103 patients had CIS (with or without Ta/T1) and 48 patients had high-grade Ta/T1 alone (without CIS). Within the CIS cohort, 55 patients (53.4%) had a complete response within 3 months of the first dose, and this response was maintained in 20 patients (36.4%) at 12 months. Within the non-CIS high-grade Ta/T1 cohort, 35 patients (72.9%) had a complete response within 3 months of the first dose and this response was maintained in 21 patients (43.8%) at 12 months. All patients without high-grade recurrence at 12 months continued to receive nadofaragene firadenovec once every 3 months.
According to results from the follow-up studies, 19.4% of the CIS cohort and 33.3% of the non-CIS high-grade Ta/T1 cohort remained free from high-grade recurrence at 24 months, the investigators reported. Among patients with CIS who had a complete response, 36.4% remained free of high-grade recurrence at 24 months. The median duration of freedom from high-grade recurrence was 12.2 months. Among patients with non-CIS high-grade Ta/T1 who were free from high-grade recurrence at 3 months, 45.7% remained free at 24 months. The median duration of freedom was 19.8 months.
For the CIS group, the cystectomy-free survival rate was 64.6% and the overall survival rate was 94.4% at 24 months, the investigators reported. For the high-grade Ta/T1 alone group, the cystectomy-free survival rate was 69.8%, and the overall survival rate was 93.2% at 24 months.
Nadofaragene firadenovec was well tolerated in both the CIS cohort and the non-CIS high-grade Ta/T1 cohort with no adverse events (AEs) leading to death. The most common drug-related AEs were instillation site discharge (24.3%), fatigue (23.4%), bladder spasm (17.8%), and urinary urgency (16.8%) of mostly grade 1 or 2. Two patients discontinued the drug due to AEs.
In the non-CIS high-grade Ta/T1 group, the most common drug-related AEs were instillation site discharge (26%), dysuria (16%), bladder spasm (14%), and micturition urgency (14%) of mostly grade 1 or 2. One patient experienced an AE leading to drug discontinuation.
“Intravesical nadofaragene firadenovec is associated with an acceptable safety profile and promising efficacy outcomes to offer a realistic alternative to chemotherapy and systemic treatment options,” according to the investigators.
Disclosure: This research was supported by FKD Therapies Oy. Please see the original references for a full list of disclosures.
Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. doi:10.1016/S1470-2045(20)30540-4
Schuckman AK, Lotan Y, Boorjian SA, Cilwa KE, Dinney CPN. Efficacy of intravesical nadofaragene firadenovec for patients with carcinoma in situ (CIS), BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC): longer-term follow-up from the phase III trial. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Poster MP16-01.
Lotan Y, Schuckman AK, Boorjian SA, Cilwa KE, Dinney CPN. Phase III trial of intravesical nadofaragene firadenovec in patients with high-grade, BCG-unresponsive, nonmuscle invasive bladder cancer: two year follow up in the TA/T1 cohort. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Poster MP16-02.