An Open-Label, Multicenter, Phase 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects with Non Muscle-Invasive Carcinoma in Situ (CIS) and/or High-Grade Papillary Disease of the Bladder Previously Treated with Bacillus Calmette-Guérin (BCG).
Bladder cancer is the 6th most common cancer in the United States, affecting more men than
women. The usual first treatment for NMIBC (Ta, T1, and CIS) is transurethral resection of
the bladder tumors followed by intravesical immunotherapy, most commonly with bacillus
Calmette-Guérin (BCG).
Because of the high risk for development of muscle invasive disease, cystectomy is
recommended for CIS and high-grade Ta and T1 patients who experience disease recurrence
following intravesical therapy. For patients unable or unwilling to undergo cystectomy,
treatment options are limited.
Vicinium contains the active pharmaceutical ingredient VB4-845, which is a recombinant fusion
protein produced in Escherichia coli (E. coli) that expresses a humanized single-chain
antibody fragment specific for the epithelial cell adhesion molecule (EpCAM) antigen linked
to ETA(252-608). Once bound to the EpCAM antigen on the surface of carcinoma cells, Vicinium
is internalized through an endocytic pathway. The ETA(252-608) is cleaved off and induces
cell death by irreversibly blocking protein synthesis.
In vitro and in vivo pharmacology demonstrated that Vicinium exhibits potent activity
[inhibitory concentration 50% (IC50) = 0.001 - 10 pM] against numerous cell lines and
effectively inhibits tumor growth in several human xenograft animal models. A Phase 2 study
evaluated once-weekly instillations of Vicinium 30 mg over 6 or 12 weeks, followed by up to 3
maintenance cycles (3 once-weekly instillations followed by a 9-week drug-free period) in 45
subjects with histologically-confirmed TCC of the bladder and residual CIS with or without
concurrent Ta or T1 who were refractory or intolerant to BCG. A complete response (defined as
no histological evidence of disease and negative urine cytology at the 3-monthly evaluations)
was achieved by 44% of subjects, and 16% of subjects remained disease-free at 1-year. A
post-study assessment found that these subjects were still disease-free at 18-25 months. The
median time to recurrence was 134 days longer in subjects who received 12 weeks of induction
therapy compared to 6 weeks.
This is an open-label, non-randomized, multicenter study in adults with NMIBC, specifically
CIS (with or without papillary disease), high-grade Ta or any grade T1 papillary disease, who
have previously failed BCG treatment (i.e., not those who are intolerant) with or without
interferon. The study consists of a Screening period, a 12-week Induction Phase, and a
Maintenance Phase of up to 21 monthly cycles for a total treatment period of up to 104 weeks.
This is an outpatient study, but all treatments are administered in the study clinic.
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