AUA 2018: Phase 3 Study of Vicinium in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: Initial Results

San Francisco, CA ( Radical cystectomy remains a major operation with significant implications on patient quality of life (QOL). For non-muscle invasive bladder cancer, especially high-grade disease, the mainstay of the therapy is intravesical BCG – while it has been demonstrated to help reduce progression to muscle-invasion, we have limited alternative options for patients who progress despite BCG. Many agents are in development, but few have demonstrated adequate efficacy and tolerability to become an established therapy. 

One agent being evaluated is Vicinium. Vicinium is a single protein drug consisting of an Epithelial Cell Adhesion Molecule (EpCAM)-specific antibody fragment fused to a potent pseudomonas toxin. After intravesical instillation, Vicinium binds EpCAM, is internalized and kills tumor cells by inhibiting protein synthesis.

Vicinium has previously been tested in phase 1 and phase II studies. In those studies, it demonstrated excellent safety and substantial clinical activity. Specifically, complete response (CR) at 3 months was found in subjects with carcinoma in situ (CIS) of 29% (Phase 1) and 40% (Phase II).

In this study, they take this agent to a phase III evaluation. The study is entitled VISTA. It is a single arm, phase III, registrational trial of Vicinium in BCG-unresponsive NMIBC. BCG-unresponsive was defined as any high grade Ta, any T1 and CIS with or without papillary disease who have completed ≥ 2 courses of full dose BCG and recurred with papillary NMIBC ≤ 30 weeks or with CIS ≤50 weeks after last BCG. Vicinium (30 mg) was then instilled into the bladder for 2 hours on the following schedule: two times/week for 6 weeks followed by weekly for 6 weeks and then every 2 weeks for up to 2 years. Subjects are evaluated every 13 weeks by urine cytology, cystoscopy and pathology of biopsy of any suspicious lesion. The primary endpoint is complete response (CR) at 3 months which requires negative cytology, normal cystoscopy, or benign/low grade Ta pathology on biopsy.

Results: They enrolled a total 133 total patients, split amongst the 3 pathology cohorts (previously described). Entire cohort was predominantly male. Most patients were in cohort 1 (CIS recurrence within 6 months of BCG) or cohort 3 (papillary recurrence within 6 months of BCG). Patients had received a median number of BCG cycles prior to treatment. 

At 3 months, patients had demonstrated a 42% CR in the CIS patients. In Cohort 1, it was 39%, and in the few patients in cohort 2 (CIS >6 months after BCG), it was 80%. In cohort 3, it was 68%. Vicinium, as previously, was well-tolerated. Only 5 (4%) had a Clavian 3+ treatment related adverse effect.  While this is just an interim analysis, they expect to have 12-month results in mid-2019.

Presented by: Rian Dickstein, MD, FACS, University of Maryland School of Medicine
Co-Authors: Ning Wu, Great Barrington, IL, Barrett Cowan, Englewood, CO, Curtis Dunshee, Tuscon, AZ, Michael Franks, Richmond, VA, Fred Wolk, Torrance, CA, Laurence Belkoff, Bala Cynwyd, PA, Sean Castelucci, Bradenton, FL, Jeffrey Holzbeierlein, Fairway, KS, Girish Kulkarni, Toronto, Canada, Alon Weizer, Ann Arbor, MI, Donald Lamm, Phoenix, AZ, David Brooks, Cambridge, MA, Jonathon Epstein, Syed Ali, Baltimore, MD, Wassim Kassouf, Montreal, Canada

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA