Nadofaragene firadenovec, a novel intravesical therapy for nonmuscle-invasive bladder cancer (NMIBC) that does not respond to bacillus Calmette- Guérin (BCG) therapy shows efficacy across important patient subgroups, investigators reported at SUO 2020, the virtual annual meeting of the Society of Urologic Oncology.

In the original phase 3 trial of 157 patients with high-grade BCG-unresponsive NMIBC, clinicians delivered nadofaragene firadenovec (also known as rAd-IFNa/Syn3), a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b, by catheter into the bladder epithelium once every 3 months. The 3-month complete response rate was 59.6% overall and 53.4% in patients with carcinoma in situ (CIS) with or without Ta or T1 tumors. In addition, 72.9% of patients with high-grade Ta or T1 tumors and no CIS had freedom from high-grade recurrence. At 12 months, 30.5% overall, 24.3% of patients with CIS (with or without Ta or T1 tumors), and 43.8% of patients with high-grade Ta or T1 tumors (and no CIS) were free from high-grade recurrence.

For both the CIS and high-grade Ta/T1 only cohorts, there were no significant differences in response rates at 3 and 15 months between male and female patients, patients younger and older than 70 years, BCG-refractory vs BCG-relapsed disease, patients with more or less than 3 prior lines of therapy, number of prior non-BCG regimens, and patients with more or less than 3 prior courses of BCG, Vikram Narayan, MD, of Emory University in Atlanta, Georgia, reported.

Continue Reading

Duration of response also did not differ significantly among groups, Dr Narayan reported. Only in the CIS cohort, patients who received 3 or fewer prior courses of BCG had significantly longer duration of response compared with patients who received more than 3 courses: 12.68 vs 4.96 months. A multivariable analysis confirmed that none of these baseline characteristics or prior therapy significantly influenced response rates at 3 and 15 months or duration of response.

“These results demonstrate the efficacy of nadofaragene firadenovec regardless of patient characteristics or prior treatment history,” Dr Narayan stated. “Nadofaragene firadenovec represents a potential novel treatment option for patients with high-grade BCG-unresponsive NMIBC that advances the current treatment paradigm.”

The FDA is currently reviewing a biologics license application (BLA) for nadofaragene firadenovec.

Disclosure: This clinical trial was supported by FKD Therapies in Oy, Finland. Please see the original reference for a full list of authors’ disclosures.


Narayan V, Boorjian S, Alemozaer M, et al. Subgroup analyses of the phase 3 study of intravesical nadofaragene firadenovec in patients with high-grade, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Presented at: SUO 2020, December 3-5, 2020. Poster 23.

Boorjian SA, Alemozaffar M, Bad 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. Published online November 27, 2020. Lancet Oncol. doi:10.1016/S1470-2045(20)30540-4

Kulkarni GS. Nadofaragene firadenovec: a new gold standard for BCG-unresponsive bladder cancer? Published online November 27, 2020. Lancet Oncol. doi:10.1016/S1470-2045(20)30586-6

TechBear. FerGene announces Landmark Phase 3 study published in Lancet Oncology [news release]. FerGene; November 30, 2020.