SUO 2019: The SUO-CTC Phase III Adstiladrin® Trial for BCG Unresponsive Non-Muscle Invasive Bladder Cancer

Washington, DC ( During the bladder cancer session at the Society of Urologic Oncology Meeting on Thursday, December 5th, Dr. Colin Dinney presented the results of a phase III clinical trial for Adstiladrin® (rAd-INFa/syn3) in BCG unresponsive non-muscle invasive bladder cancer.

Adstiladrin is a non-replicating adenovirus vector harboring recombinant IFN alpha2b with antitumor activity. Following intravesical administration, the virus is transduced into the lining of the bladder. The IFN alpha2b gene is incorporated into the cellular DNA resulting in the synthesis and expression of large amounts of IFN alpha2b protein resulting in antineoplastic activity. Previous clinical trials have demonstrated that it is both safe and effective in BCG-refractory and recurrent NMIBC.

This Phase III study was designed to explore the use of high dose Adstiladrin in patients with high-grade NMIBC who are unlikely to benefit from further intravesical BCG. 151 patients were enrolled, including 103 with CIS and 48 with papillary disease. The primary endpoint was complete response rate at 3 months in patients with CIS with over half the participants achieving this end point (3-month CR=53%). Interestingly, all complete responses were achieved within the first 3 months, allowing for early recognition of responders. At 12 months, 24% of patients still demonstrated a complete response. This compares very favorably with the 10% 12-month complete response rate reported for Valrubicin; the only approved agent in this arena. Even greater success was reported for patients with papillary NMIBC (12-month CR=43%).

Additional secondary endpoints included toxicity and recurrence free survival (RFS). Overall, Dr. Dinney reported that the medication was well tolerated. There were no grade 4 or 5 toxicities reported, with only 1 drug and 2 procedure related adverse events. No immune related adverse events were observed and only 3 participants (1.9%) stopped the medication secondary to treatment effects. At 3 months follow up, high grade RFS was 53% and 73% in patients with CIS and papillary disease, respectively. With longer follow up, high grade RFS declined to 24% and 44% at 1 year, with recurrence becoming very rare thereafter.

Overall, the presentation provided promising results regarding a novel therapy for a challenging clinical space, however, longer follow-up results are still needed.


Primary endpoint—Incidence of CR at any time in patients with CIS

Secondary Endpoint—Incidence of HG RFS and Durability of Response Identifier: NCT02773849

Presented by: Colin Dinney, MD, Department Head, Chairman, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, W.A. "Tex" & D. Moncrief, Jr. Co-Chair, Genitourinary Steering Committee - Bladder Task Force, Houston, TX, MD Anderson Cancer Center

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019,  Washington, DC

Further Related Content: FerGene announces pivotal Phase 3 study of nadofaragene firadenovec met its primary endpoint with more than half of patients with high-grade non-muscle invasive bladder cancer (CIS ± Ta/T1) achieving a complete response at three months

AUA 2019: Nadofaragene firadenovec (Adstiladrin®) — Late-Breaking Phase 2 Data for Patients with High-grade, BCG Refractory or Relapsed Non-muscle Invasive Bladder Cancer