PD03-02 PHASE 3 RESULTS OF VICINIUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Non-invasive I (PD03)1 Apr 2020PD03-02 PHASE 3 RESULTS OF VICINIUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER Neal Shore*, Michael O'Donnell, Thomas Keane, Michael A.S. Jewett, Girish S. Kulkarni, Rian Dickstein, Fred Wolk, Curtis Dunshee, Laurence Belkoff, Rachelle L. Dillon, Jeannick Cizeau, and Wassim Kassouf Neal Shore*Neal Shore* , Michael O'Donnell Michael O'Donnell , Thomas Keane Thomas Keane , Michael A.S. JewettMichael A.S. Jewett , Girish S. KulkarniGirish S. Kulkarni , Rian DicksteinRian Dickstein , Fred WolkFred Wolk , Curtis DunsheeCurtis Dunshee , Laurence BelkoffLaurence Belkoff , Rachelle L. DillonRachelle L. Dillon , Jeannick CizeauJeannick Cizeau , and Wassim Kassouf Wassim Kassouf View All Author Informationhttps://doi.org/10.1097/JU.0000000000000823.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Alternatives to radical cystectomy (RC) are critically needed for the treatment of high-risk BCG-unresponsive NMIBC. Vicinium is a recombinant fusion protein comprised of an anti-EpCAM scFv linked to a variant of Pseudomonas exotoxin A (ETA). ETA mediates tumor cell death by blocking protein synthesis. Dying tumor cells display immunogenic cell death signals and neo-antigens known to promote an adaptive T-cell mediated anti-tumor response. Vicinium is being developed for the treatment of BCG-unresponsive NMIBC. METHODS: BCG-unresponsive NMIBC patients defined as refractory or relapsing within 6 months (n = 126) and relapsing within 6 to 11 months (n = 7) after adequate BCG therapy were accrued in a Phase 3 single-arm multicenter registrational trial (NCT02449239). During induction, Vicinium was instilled for 2 hours twice weekly for 6 weeks, then weekly for 6 weeks. Disease-free patients at 3 months received maintenance every 2 weeks for up to 2 years. Patients were assessed every 13 weeks, with a response defined as negative cytology along with normal cystoscopy or absence of high-grade disease on biopsy. RESULTS: As of May 29th 2019, the complete response rate of the evaluable carcinoma in situ (CIS) patients (n = 89) at 3 months was 40% and the median duration of response was 9.4 months (95% CI, 5.1-NE). Of the 3-month CIS responders, 52% remained disease-free for 12 months after starting treatment. The recurrence-free rates of the evaluable papillary patients (n = 38) at 3, 6, 12 and 24 months were 71, 58, 50 and 37%, respectively, and the median time to recurrence was 13.2 months (95% CI, 5.6-NE). Overall, responders at 3 months remained RC-free for 34.0 vs. 20.7 months for non-responders (p ≤ 0.001). Furthermore, the rate of RC was only 10% (6 of 63) for the 3-month responders versus 32% (18 of 56) for the non-responders. Preliminary overall survival was 96% (95% CI, 92-100) at 2 years. Vicinium was well-tolerated with only 52% of patients experiencing treatment-related adverse events (AEs), the majority being grade 1-2. Moreover, the AE frequency was similar between 54-69, 70-79 and 80-plus age groups. A total of 4 treatment-related severe AEs were reported in 3 patients and included grade 4 cholestatic hepatitis, grade 5 renal failure, grade 3 acute kidney injury and grade 2 pyrexia. Only 3% of the patients discontinued treatment due to AEs. CONCLUSIONS: This Phase 3 study showed that Vicinium was well-tolerated, demonstrated clinically meaningful anti-tumor activity and may delay and/or prevent RC. Source of Funding: Sesen Bio © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e72-e72 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Shore* More articles by this author Michael O'Donnell More articles by this author Thomas Keane More articles by this author Michael A.S. Jewett More articles by this author Girish S. Kulkarni More articles by this author Rian Dickstein More articles by this author Fred Wolk More articles by this author Curtis Dunshee More articles by this author Laurence Belkoff More articles by this author Rachelle L. Dillon More articles by this author Jeannick Cizeau More articles by this author Wassim Kassouf More articles by this author Expand All Advertisement PDF downloadLoading ...

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