Nadofaragene Firadenovec Induces Durable Activity in High-Risk, BCG-Unresponsive NMIBC With CIS

November 29, 2023

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Nadofaragene firadenovec-vncg led to encouraging rates of high-grade recurrence-free survival and overall survival in patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors.

Stephen A. Boorjian MD

Nadofaragene firadenovec-vncg (Adstiladrin) led to encouraging rates of high-grade recurrence-free survival (RFS) and overall survival (OS) in patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1), according to new interim findings from the 36-month analysis from the single-arm phase 3 Study CS-003 (NCT02773849).¹

“These new data continue to build on the body of evidence supporting the efficacy and safety of [nadofaragene firadenovec], adding to the data on its sustained durable response following treatment,” Elizabeth Garner, MD, MPH, chief scientific officer at Ferring Pharmaceuticals, US, stated in a news release. “Patients with BCG-unresponsive NMIBC are at high risk for recurrence and disease progression, which can often lead to bladder removal surgery, or cystectomy. [Nadofaragene firadenovec] is an innovative therapy that we believe will transform the current standard of care for these patients, providing an effective alternative therapy.”

In December 2022, nadofaragene firadenovec became the first gene therapy to receive an indication for the treatment of patients with high-risk, BCG-unresponsive NMIBC with CIS with or without papillary tumors.²

The regulatory decision was based on data from the open-label, multicenter Study CS-003, in which the intravesical therapy led to a 3-month complete response (CR) rate of 51% (n = 50/98; 95% CI, 41%-61%) in patients with CIS with or without concomitant high-grade Ta or T1 disease.³ The 12-month rate of high-grade RFS among patients who achieved CR was 46% (n = 23). The median duration of response (DOR) was 9.7 months (range, 3-52+).

CR in patients with CIS with or without concomitant high-grade Ta or T1 papillary disease served as the primary end point of the trial.⁴ Secondary end points included duration of CR, event-free survival (EFS), duration of EFS, cystectomy incidence, OS, anti-adenoviral antibody levels, safety, and DOR during the long-term follow-up period.

Eligible patients received 75 mL of an intravesical instillation of nadofaragene firadenovec (3 x 1011 vp) once every 3 months for up to 12 months or until unacceptable toxicity or recurrent high-grade NMIBC.¹ Patients without documented high-grade recurrence were allowed to continue nadofaragene firadenovec every 3 months as part of an ongoing follow-up analysis.

Updated results showed that 25.5% (n = 14/55) of patients who continued treatment after the 12-month mandated treatment period remained free from high-grade recurrence at 36 months after the start of treatment. The estimated probability of duration of CR at 12, 24, and 36 months was 46.5%, 36.6%, and 34.2%, respectively.

In the overall patient cohort (n = 103), the estimated median duration of high-grade recurrence-free survival was 6 months (95% CI, 3.4-8.3), with an estimated 12-month high-grade RFS rate of 30.1% (95% CI, 21.55%-39.2%). Additionally, the estimated 36-month cystectomy-free survival rate was 53.8% (95% CI, 43.3%-63.1%), and the 3-year OS rate was 90.4% (95% CI, 82.3%-94.9%).

Regarding safety, 2 patients (1.9%) discontinued nadofaragene firadenovec because of adverse effects. Four patients (3.9%) developed progression to muscle-invasive disease.

The follow-up analysis will continue with a planned 5-year treatment and monitoring phase.

“The management of patients with continued high-grade NMIBC after treatment with BCG remains challenging,” Stephen A. Boorjian MD, the Carl Rosen Professor and David and Anne Luther Chair of the Department of Urology at Mayo Clinic in Rochester, Minnesota, stated. “These new [nadofaragene firadenovec] data emphasize the importance of obtaining long-term follow up from novel therapies to establish treatment expectations.”