Nadofaragene firadenovec published data show strong efficacy in BCG-unresponsive NMIBC

“These data published in the Lancet Oncology show that nadofaragene firadenovec, a first-of-its-kind therapy, may be an effective treatment option for BCG-unresponsive non-muscle invasive bladder cancer patients,” Colin P. N. Dinney, MD.

Nadofaragene firadenovec induced complete responses (CRs) in over half of patients with high-grade, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), according to phase 3 data now published in the Lancet Oncology.1,2

In patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1), the CR rate with nadofaragene firadenovecwas 53.4% at 3 months. The 12-month CR rate was 24.3% and the median duration of CR was 9.69 months.

“Once patients with high-grade, non-muscle invasive bladder cancer no longer benefit from their initial BCG treatments, patients often make an informed decision to decline cystectomy—a highly complex and life-altering bladder removal surgery—or are often medically ineligible for this complex operation, leaving them with limited options,” Colin P. N. Dinney, MD, chairman, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, and senior author of the publication, stated in a press release.

“These data published in the Lancet Oncology show that nadofaragene firadenovec, a first-of-its-kind therapy, may be an effective treatment option for BCG-unresponsive non-muscle invasive bladder cancer patients,” added Dinney.

The multicenter, open-label, repeat-dose phase 3 study (NCT02773849) accrued patients with BCG-unresponsive NMIBC at 33 clinical sites in the United States. Among 157 treated patients, there were 107 patients with CIS ± Ta/T1 tumors. The median patient age in this group was 72 years (range, 66-77), 89% were male, 93% were white, and the median time from initial bladder cancer diagnosis was 20 months (range, 13-35).

Overall, 90.7% of patients had an ECOG performance score of 0, and 3.7% had prior radiotherapy. The number of prior BCG courses included 1 (0.9%), 2 (42.1%), 3-8 (53.3%), and ≥9 (3.7%).

The novel intravesical gene-mediated therapy nadofaragene firadenovec was administered by catheter as a single dose into the bladder. Those patients without recurrence received repeat doses at 3, 6, and 9 months. The primary end point was the CR rate in patients with CIS± Ta/T1 tumors.

Of the 107 patients with CIS± Ta/T1 disease, 103 were included in the efficacy analysis (4 patients were excluded because they did not meet the study definition of BCG-unresponsive NMIBC). Among these 103 patients, 55 (53.4%) had a CR at month 3, and 25 (24.3%) were in CR at 12 months.

“As a practicing urologist, I’m encouraged by these efficacy and safety data which demonstrate the potential for a novel treatment option that fits within the urology practice and gives patients the choice of receiving treatment once every 3 months—which may be a particularly important consideration in this evolving healthcare environment,” Gennady Bratslavsky, MD, president of the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC), and professor and chair of Urology at SUNY Upstate Medical University, stated in the press release. “Our organization is proud to have played a key role in the mid- and late-stage clinical studies for nadofaragene firadenovec.”

The safety analysis included all 157 patients enrolled on the trial who received at least 1 dose of nadofaragene firadenovec. The most common grade 3 treatment-related adverse event (TRAE) was micturition urgency, which occurred in 2 patients. There were four other grade 3 TRAEs occurring in 1 patient each: bladder spasm, syncope, hypertension, and urinary incontinence.No grade 4 TRAEs were reported and there were no treatment-related deaths.

The trial remains ongoing with the study design set up for a 4-year treatment and monitoring phase.

In their study summary, the authors wrote, “Future research [of nadofaragene firadenovec] should include analyses to help to identify early treatment responders and provide insights into the potential mechanisms of treatment non-response.


1. FerGene announces Landmark Phase 3 study published in Lancet Oncology. Published online November 30, 2020. Accessed November 30, 2020.

2. 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