Adofaragene firadenovec effective in BCG-unresponsive papillary NMIBC

A study investigating nadofaragene firadenovec for high-grade, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) achieved encouraging, durable, high-grade, recurrence-free survival.

Responses remained durable for at least one year

A multicentre, open-label Phase-3 study investigating nadofaragene firadenovec for high-grade, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) achieved encouraging, durable, high-grade, recurrence-free survival.

Dr. Neal Shore (Carolina Urologic Research Center, USA) presented the outcomes of the papillary disease (PD) cohort from the trial [1]. Nadofaragene firadenovec is a novel intravesical-administered adenovirus-mediated gene therapy (rAd-IFN) delivering the human interferon (IFN) α2b gene. When combined with the excipient Syn3, rAd-IFN/Syn3 has been shown in a phase-2 trial to be well tolerated and to lead to sustained localized IFNα2b gene expression.

The phase-3 trial enrolled 157 patients (mean age 71 years), 50 of whom had PD. Intravesical administration of nadofaragene firadenovec (3×1,011 viral particles/mL [75 mL]) was planned every 3 months for up to 4 doses during 12 months. All patients with an absence of high-grade disease recurrence at month 12 were offered continued treatment every 3 months. The primary endpoint was complete response (CR) at any time for the carcinoma in situ cohort (CIS ± Ta/T1, or PD [Ta/T1 alone]) unresponsive to BCG. Key secondary endpoints included the rate and durability of high-grade recurrence-free survival as well as safety in patients with PD.

The efficacy population consisted of 48 patients with PD. Of those, 35 (72.9%) achieved recurrence-free survival at 3 months, 30 (62.5%) at 6 months, 28 (58.3%) at 9 months, and 21 (43.8%) at 12 months. The primary endpoint was met; 55 (n=103; 53.4%; 95% CI 43.3-63.3) patients in the CIS cohort achieved CR during the 12-month period. The total cohort (n=151) had 59.6% CR, whereas 72.9% of the PD subgroup (n=48) achieved CR. All CRs occurred in the first 3 months. Patients with CIS demonstrated 24.3% HGRF at month 12, 43.8% of PD patients. In PD patients, the median duration of HGRF was 12.35 months (95% CI 6.67, months-not reached).

The most common drug-related treatment-emergent adverse events were instillation site discharge (33.1%), fatigue (23.6%), bladder spasm (19.7%), micturition urgency (17.8%), and hematuria (16.6%). No patient died.

In short, nadofaragene firadenovec demonstrated clinical response in patients with high-grade BCG-unresponsive NMIBC for both CIS and PD cohorts. Responses remained durable for at least one year, and the safety profile and dosing schedule were acceptable. “These data represent a significant therapeutic advancement for BCG-unresponsive patients”, concluded Dr. Shore.

1. Shore N, et al. Results from the phase III study of nadofaregene firadenovec: Safety and efficacy in patients (pts) with high-grade, BCG-unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). EAU20 Virtual Congress, 17-26 July 2020, Game-Changing Session 2.

Esanum is an online network for approved doctors

Esanum is the medical platform on the Internet. Here, doctors have the opportunity to get in touch with a multitude of colleagues and to share interdisciplinary experiences. Discussions include both cases and observations from practice, as well as news and developments from everyday medical practice.

Esanum ist ein Online-Netzwerk für approbierte Ärzte

Esanum ist die Ärzteplattform im Internet. Hier haben Ärzte die Möglichkeit, mit einer Vielzahl von Kollegen in Kontakt zu treten und interdisziplinär Erfahrungen auszutauschen. Diskussionen umfassen sowohl Fälle und Beobachtungen aus der Praxis, als auch Neuigkeiten und Entwicklungen aus dem medizinischen Alltag.

Esanum est un réseau en ligne pour les médecins agréés

Esanum est un réseau social pour les médecins. Rejoignez la communauté et partagez votre expérience avec vos confrères. Actualités santé, comptes-rendus d'études scientifiques et congrès médicaux : retrouvez toute l'actualité de votre spécialité médicale sur esanum.