Vicinium Shows Encouraging CR Rate in High-Risk NMIBC Trial, Moving Towards BLA Submission

Thomas Cannell, DVM

Thomas Cannell, DVM

Vicinium has demonstrated positive 12-month complete response (CR) rate findings in the VISTA trial of patients with high-risk patients with non—muscle-invasive bladder cancer (NMIBC) who were unresponsive to bacillus Calmette-Guérin (BCG) treatment, according to updated preliminary findings from the phase III clinical trial.¹

Across 2 of the 3 patient cohorts, patients with carcinoma in situ who had received prior BCG therapy demonstrated a CR rate of 28% (95% CI, 19%-39%) at 6 months and 17% (95% CI, 10%-26%) at 12 months. CR rate is one of the primary endpoints of the VISTA trial.

Sesen Bio, the developer of Vicinim, announced in a press release that these findings will serve as the basis on a biologics license application (BLA) submission to the FDA in the fourth quarter of 2019 for a potential accelerated approval.

“After 2 very positive meetings with the FDA in the second quarter, we are now focused on initiating the BLA submission for Vicinium in the fourth quarter under an accelerated approval pathway with rolling review,” said Thomas Cannell, DVM, president and chief executive officer of Sesen Bio, in the press release. “We believe this regulatory pathway and our strong 12-month phase III data could potentially expedite patient access to Vicinium, which is particularly important in light of the ongoing BCG shortage.”

Vicinium is a protein fusion drug consisting of an epithelial cell adhesion molecule (EpCAM)-specific antibody fragment fused toPseudomonasExotoxin A, a potent inhibitor of protein synthesis.

VISTA is an open-label, multicenter, single-arm phase III trial exploring the efficacy and tolerability of the monotherapy in a high-risk population of patients with NMIBC who were unresponsive to BCG treatment (NCT02449239).

Patients in the trial were adults with carcinoma in situ and/or high-grade (Ta and T1) papillary disease who were unresponsive to prior treatment with BCG with or without interferon. Participants must have completed at least 2 courses of full-dose BCG, with at least 5 doses in the first course and 2 doses in the second course, and experienced disease recurrence within 30 weeks from last BCG treatment for those with papillary NMIBC, or within 50 weeks for those with CIS.²

The outpatient VISTA trial consists of a screening period, a 12-week induction phase, and a maintenance phase of up to 21 cycles of treatment, for a total of 104 weeks of treatment. The 133 patients were also divided into 1 of 3 cohorts: those with carcinoma in situ with or without papillary disease that was refractory or the patient had recurred within 6 months of adequate BCG treatment, those with carcinoma in situ with or without papillary disease that recurred between 6 and 11 months of BCG treatment, and patients with papillary disease only that recurred within 6 months of BCG treatment.

Vicinium at 30 mg in 50 mL of saline was instilled into the bladder 2 hours on a schedule of 2 times per week for 6 weeks in the induction phase, followed by weekly for 6 weeks followed by every 2 weeks for up to 2 years as the maintenance phase.

The primary endpoints of the trial are CR rate and the duration of response (DOR) in the first cohort. Secondary endpoints include time to disease recurrence in the third cohort as well as time to cystectomy, progression-free survival, event-free survival, and overall survival across all 3 cohorts.

According to earlier findings from the phase III trial, more than 95% of screened NMIBC samples expressed EpCAM. Additionally, the treatment was well tolerated, with adverse events (AEs) noted in 46% of patients. The most common AEs were dysuria (12%), urinary tract infection or pollakiuria (10%), and hematuria (7%). Three treatment-related serious AEs were observed, including renal failure with cholestatic hepatitis in one patient and acute kidney injury in another patient that recovered.²

Updated preliminary findings showed that in the first cohort of 82 evaluable patients who completed the induction phase, the CR rate was 39% at 3 months, 26% at 6 months, and 17% at 12 months. In the second cohort of 7 evaluable patients who completed the induction phase, the CR rate was 57% at 3 months, 57% at 6 months, and 14% at 12 months.¹

In the first cohort, the median DOR was 273 days (95% CI, 122-not available [NA]) among 86 patients. An ad-hoc analysis of patients from both cohorts 1 and 2 (n = 93) showed that among patients who achieved a CR at 3 months, 52% had a CR for 12 months or more.

The median time to disease recurrence in patients in the third cohort (n = 40) was 402 days (95% CI, 170-NA).

Across the 3 cohorts, more than 75% of patients treated with Vicinium were estimated to remain cystectomy-free at 3 years, 90% were estimated to remain progression-free for 2 years or more, 29% were estimated to remain event free at 1 year, and 96% were estimated to have an overall survival of 2 years or more.

Updated safety findings showed that 95% of all AEs were grade 1 or 2. Serious AEs were observed in 14% of patients. Four patients discontinued treatment due to an AE.

An Oncologic Drugs Advisory Committee meeting is expected to occur after the BLA is submitted to review the risk-benefit profile of Vicinium.

The FDA had also granted a fast track designation to Vicinium last August for the treatment of patients with BCG-unresponsive, high-grade NMIBC.

References

1. Sesen Bio Reports Positive, Preliminary Data Update from Phase 3 VISTA Trial for High-Risk Non-Muscle Invasive Bladder Cancer [press release]. Cambridge, MA: Sesen Bio; August 8, 2019. https://bit.ly/2OM9LEB. Accessed August 9, 2019.
2. Dickstein R, Wu N, Cowan B, et al. Phase 3 study of Vicinium in BCG-unresponsive non-muscle invasive bladder cancer: initial results.J Urol. 2018;199(4S; abstr LBA27):e1167. doi: 10.1016/j.juro.2018.03.099.