Phase III trial of Instiladrin shows efficacy for invasive bladder cancer.- FerGene Inc

FerGene Inc. announced new data analyses results from the landmark Phase III clinical trial evaluating Instiladrin or rAd-IFN/Syn3 (nadofaragene firadenovec) for the treatment of patients with high-grade, Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). In the study, published in The Lancet Oncology on November 27, patients received nadofaragene firadenovec, an intravesical therapy given once every three months that is believed to target the patient’s own bladder wall cells to enhance the body’s natural defenses to fight cancer. The three new analyses from the pivotal study presented during the Society of Urologic Oncology (SUO) 21st Annual Meeting provide more evidence that nadofaragene firadenovec is a promising option for patients where BCG has failed. The incidence and time to cystectomy was a key secondary objective of the Phase III study. A total of 40 (26.5%) patients underwent cystectomy, including 30 (29.1%) in the CIS +Ta/T1 cohort with median time to cystectomy being 8.87 months, and 10 (20.8%) in the HG Ta/T1 cohort with median time to cystectomy being 8.31 months. Patients who achieved complete response (CR) had significantly longer median time to cystectomy compared to those who did not (p=0.0432; 11.35 vs. 6.36 months, respectively. The estimated cystectomy-free survival among all treated patients was 64.5% at 24 months and was similar between the cohorts. The most common adverse events (AEs) observed in the Phase III study that occurred in patients in order of decreasing frequency were: instillation site discharge, fatigue, bladder spasm, micturition urgency, and hematuria. The discontinuation rate due to AEs was 1.9%.The post hoc subgroup analysis of the Phase III study in high-grade, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were based on the efficacy population of 151 patients. There were no significant differences in response rate at 3 and 15 months between males and females, age groups, BCG-refractory vs. BCG-relapsed, <3 or>3 prior course of BCG. There were also not significant differences between the subgroups in duration of response, except in the CIS+Ta/T1 cohort, where patients had received <3 prior courses of bcg had significantly longer duration of response compared to patients who received>3 courses (12.68 vs 4.96 months; p=0.0172).Of the 151 patients included in the analysis for this secondary objective,129 had anti-adenoviral antibody titer results and were included in this analysis. Among the 55 patients who achieved CR in the CIS+Ta/T1cohort, significantly more patients had positive post-baseline immunogenic response (43 vs. 8; p=0.0033). Similar results were found in the high-grade Ta/T1 cohort where among the 34 patients who remained free of high-grade recurrence at 3 months, significantly more patients had positive post-baseline immunogenic response (30 vs. 4; p=0.0003). At 15 months, the same trends were noted although the differences were not significant.See: "Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial." Stephen A Boorjian et al. The Lancet November 27, 2020DOI:https://doi.org/10.1016/S1470-2045(20)30540-4