LBA27 PHASE 3 STUDY OF VICINIUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER: INITIAL RESULTS (2018)

You have accessJournal of UrologyPlenary: Next Frontier1 Apr 2018LBA27 PHASE 3 STUDY OF VICINIUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER: INITIAL RESULTS Rian Dickstein, Ning Wu, Barrett Cowan, Curtis Dunshee, Michael Franks, Fred Wolk, Laurence Belkoff, Sean Castelucci, Jeffrey Holzbeierlein, Girish Kulkarni, Alon Weizer, Donald Lamm, David Brooks, Jonathon Epstein, Syed Ali, and Wassim Kassouf Rian DicksteinRian Dickstein , Ning WuNing Wu , Barrett CowanBarrett Cowan , Curtis DunsheeCurtis Dunshee , Michael FranksMichael Franks , Fred WolkFred Wolk , Laurence BelkoffLaurence Belkoff , Sean CastelucciSean Castelucci , Jeffrey HolzbeierleinJeffrey Holzbeierlein , Girish KulkarniGirish Kulkarni , Alon WeizerAlon Weizer , Donald LammDonald Lamm , David BrooksDavid Brooks , Jonathon EpsteinJonathon Epstein , Syed AliSyed Ali , and Wassim KassoufWassim Kassouf View All Author Informationhttps://doi.org/10.1016/j.juro.2018.03.099AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Alternatives to radical cystectomy are critically needed in patients with non-muscle invasive bladder cancer (NMIBC) that is unresponsive to Bacillus Calmette-Guerin (BCG). 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 had excellent safety and substantial clinical activity in Phase 1 and 2 studies with a complete response at 3 months in subjects with carcinoma in situ (CIS) of 29 and 40%, respectively. The objectives of this study include testing efficacy of Vicinium in subjects with BCG unresponsive NMIBC. METHODS VISTA is a single arm, phase III, registrational trial of Vicinium in BCG-unresponsive NMIBC (high grade Ta, any T1 and CIS with or without papillary disease) (NCT02449239). Subjects must have completed ≥ 2 courses of full dose BCG and recurred with papillary NMIBC ≤ 30 weeks or with CIS ≤50 weeks after last BCG. Vicinium (30mg) is 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 at 3 months which requires negative cytology, normal cystoscopy, or benign/low grade Ta pathology on biopsy. RESULTS Herein, we report on the 75 subjects with CIS out of 110 total enrolled (35 with papillary only NMIBC) as of December 2017 data cut-off. By immunohistochemistry > 95% of screening NMIBC samples expressed EpCAM, the target of Vicinium. Vicinium was well tolerated: 46% of subjects had adverse events related to study drug, the most common being dysuria (12%), UTI or pollakiuria (10%) and hematuria (7%). Three treatment-related SAEs included renal failure (CTCAE Grade 5) with cholestatic hepatitis (Grade 4) in one subject and recovered acute kidney injury (Grade 3) in another. The 3 month complete response rate in subjects with CIS ± papillary of the fully enrolled, pivotal trial will be presented for the first time. CONCLUSIONS VISTA study design is closely aligned with the 2018 FDA final drug development guidance in BCG unresponsive NMIBC. Vicinium is a well-tolerated and active agent in subjects with BCG unresponsive NMIBC. The BCG-like administration regimen has potential to provide an important alternative to radical cystectomy for patients and urologists alike. © 2018FiguresReferencesRelatedDetailsCited byNazmifar M, Williams C, Naser-Tavakolian A, Heard J, Rosser C, Theodorescu D and Ahdoot M (2022) Clinical and Preclinical Therapies for Bladder Cancer Following Bacillus Calmette-Guérin FailureJournal of Urology, VOL. 209, NO. 1, (32-48), Online publication date: 1-Jan-2023.Wymer K, Sharma V, Saigal C, Chamie K, Litwin M, Packiam V, Mossanen M, Pagliaro L, Borah B and Boorjian S (2020) Cost-Effectiveness Analysis of Pembrolizumab for Bacillus Calmette-Guérin-Unresponsive Carcinoma In Situ of the BladderJournal of Urology, VOL. 205, NO. 5, (1326-1335), Online publication date: 1-May-2021.Meng M, Gschwend J, Shore N, Grossfeld G, Mostafid H and Black P (2019) Emerging Immunotherapy Options for bacillus Calmette-Guérin Unresponsive Nonmuscle Invasive Bladder CancerJournal of Urology, VOL. 202, NO. 6, (1111-1119), Online publication date: 1-Dec-2019. Volume 199Issue 4SApril 2018Page: e1167 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Rian Dickstein More articles by this author Ning Wu More articles by this author Barrett Cowan More articles by this author Curtis Dunshee More articles by this author Michael Franks More articles by this author Fred Wolk More articles by this author Laurence Belkoff More articles by this author Sean Castelucci More articles by this author Jeffrey Holzbeierlein More articles by this author Girish Kulkarni More articles by this author Alon Weizer More articles by this author Donald Lamm More articles by this author David Brooks More articles by this author Jonathon Epstein More articles by this author Syed Ali More articles by this author Wassim Kassouf More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...