ASCO GU 2020: Phase 3 Trial Results - Safety and Efficacy of Intravesical Nadofaragene Firadenovec for patients with High-Grade, BCG Unresponsive Nonmuscle Invasive Bladder Cancer (NMIBC)

San Francisco, CA ( The majority of bladder cancer is non-muscle invasive at the time of diagnosis. Intravesical BCG is standard of care for high grade disease, however, up to 40% will fail to respond, and these patients carry an increased risk of recurrence and progression. While some can be rescued with an additional cycle of BCG, early cystectomy is recommended for refractory cases. While cystectomy can be curative, many such patients (pts) are unwilling or unable given the associated morbidity of surgery. For this reason, BCG refractory NMIBC is an active area of drug development. Dr. Stephen Boorjian presented the results of a Phase III trial of intravesical nadofaragene firadenovec for patients with high-grade, BCG unresponsive nonmuscle invasive bladder cancer.


Nadofaragene firadenovec is an intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in IFNα2b expression. Previous, phase 2 trials have demonstrated a durable response in this population. In a multicenter, open-label Phase 3 study, the investigators administered the medication once every 3 months for up to 4 doses. They evaluated the below endpoints and enrolled a total of 157 patients


Among pts with CIS (n=103), 55 (53.4%) (95% CI, 43.3-63.3) achieved a complete response. Most notably, all complete responses were obtained within 3 months of treatment. Of these, nearly half remained free of high-grade recurrence at 12 months, 25 (45.5%). As for the secondary endpoint, durability was also promising for patients with high grade Ta/T1, 35 (72.9%) and 21 (43.8%) were free from recurrence at 3 and 12mos, respectively. Most treatment-emergent adverse events (TEAEs) were transient in nature: installation site discharge 33.1%; fatigue 23.6%; bladder spasm 19.7%; micturition urgency 17.8%; hematuria 16.6%.


Overall, Nadofaragene achieved a complete response in the majority of patients with BCG-unresponsive CIS and was well tolerated. Additionally, there was early differentiation between responders and non-responders and the responses demonstrated good durability. These data represent a potentially significant management advancement for a historically difficult to treat disease state.

Clinical trial information: NCT02773849

Presented by: Stephen A. Boorjian, MD, Urologist, Mayo Clinic, Rochester, Minnesota

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California