This was a Phase II multicenter study targeting BCG unresponsive high grade NMIBC patients and refused to undergo radical cystectomy were randomized to one of two different Instiladrin viral particle dosages for their disease. The patients received treatments every 3 months for a total of 4 treatments if they continued to respond to therapy without a recurrence.
Instiladrin is a non-replicating recombinant adenovirus vector containing the human interferon alpha-2b gene. It is administered intravesically and serves as a gene transfer vector and is formulated with Syn3, a polyamide surfactant that enhances the adenoviral transduction of the bladder lining. This allows for more reliable viral transduction of the IFNα-2b gene and ultimately production of IFNα-2b in the bladder. IFNα-2b is believed to be a key early cytokine in the immune response initiated by BCG and Instiladrin allows for more reliable production of this cytokine.
The primary endpoint was freedom from high grade recurrence-free survival (RFS) at 12 months defined by negative bladder biopsies.
The disease states of the 40 patients consisted of 21 pure CIS, 4 CIS + Ta, 5 CIS + T1, 4 Ta, and 6 T1. Overall, the 12-month high grade RFS was 35% and was comparable between the two groups that only differed in the number of viral particles received. RFS at 12 months was highest in Ta or T1 patients at 50% and lowest in pure CIS patients at 29%. On long-term follow-up, seven patients who recurred with disease on the trial died within a median of 16 months. Although none of the deaths was thought to be treatment-related, at least two of the deaths were due to disease progression. The most common treated-related adverse events (AEs) were urgency (40%), dysuria (40%), and fatigue (33%). However, none of the patients experienced grade 4-5 AEs.