Mp16-20 Final Results of a Phase I, Single-Arm Clinical Trial of the Combination of Durvalumab and Vicineum in BCG Unresponsive, High-Risk Non-Muscle-Invasive Bladder Cancer Patients (Nct03258593)

You have accessJournal of UrologyBladder Cancer: Non-invasive I (MP16)1 May 2024MP16-20 FINAL RESULTS OF A PHASE I, SINGLE-ARM CLINICAL TRIAL OF THE COMBINATION OF DURVALUMAB AND VICINEUM IN BCG UNRESPONSIVE, HIGH-RISK NON-MUSCLE-INVASIVE BLADDER CANCER PATIENTS (NCT03258593) Genesis Rivera-Marquez, Beatriz Walter, Rebecca Dolan, Sonia Belfield, Maria Merino, Sandeep Gurram, Andrea Apolo, Scot Niglio, Piyush Agarwal, and Vladimir A. Valera Genesis Rivera-MarquezGenesis Rivera-Marquez , Beatriz WalterBeatriz Walter , Rebecca DolanRebecca Dolan , Sonia BelfieldSonia Belfield , Maria MerinoMaria Merino , Sandeep GurramSandeep Gurram , Andrea ApoloAndrea Apolo , Scot NiglioScot Niglio , Piyush AgarwalPiyush Agarwal , and Vladimir A. ValeraVladimir A. Valera View All Author Informationhttps://doi.org/10.1097/01.JU.0001008640.01272.9d.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy remains the gold standard for the treatment of high-risk, non-muscle invasive bladder cancer (NMIBC) that fails to respond to intravesical treatment with BCG. Some patients are unfit or refuse this therapeutic option. Therefore, there is an unmet clinical need for alternative treatments in this population. The combination of new and alternative intravesical therapies with or without systemic agents has emerged as the new treatment paradigm. In this study, we aimed to evaluate the safety and tolerability of clinical trial that combined Vicineum and Durvalumab in BCG-unresponsive NMIBC. METHODS: Data from a single institution, phase I study using a combined regimen that included the intravesical administration of a fusion protein containing an antibody fragment against EpCAM linked to a truncated Pseudomonas Exotoxin A (Oportuzumab Monatox, Vicineum) together with the systemic PDL-1 inhibitor Durvalumab was evaluated. Twelve-week response was evaluated by cytology and mandatory biopsy. Treatment related adverse events (TrAE) were recorded as primary objective (safety and tolerability). Secondary objectives included correlatives analysis of response such as urinary EpCAM, PD-L1/PD-1, plasma cytokine expression, as well as recurrence-free survival. RESULTS: Fifteen patients were ultimately enrolled from an expected 24 patient accrual. Ninety-three per cent were male. Mean age at enrollment was 72 years (range 52-83 years). Seven patients (47%) had HG Ta disease, 20% were HG T1 (3/15) and 5 (33%) had Tis at enrollment. Seven patients (47%) were disease free at first 12-week evaluation and 6/15 (40%) at 6 months. Of these, three patients have remained with no evidence of disease for >12 months. All 15 patients showed at least 1 treatment related adverse event and 27% were grade 3 or higher. The most common adverse events were related to voiding symptoms and hematuria. On biomarker analysis, a decrease in urinary EpCAM and a 5-10 fold increase in PD-L1 at week 3-5 was observed. Median recurrence-free survival was 13.2 months (12.28 NR). CONCLUSIONS: The combination of Vicineum and Durvalumab was safe and well tolerated and had a 12-week response rate of almost 50%, with a prolonged (>12 months) benefit in some patients with high risk NMIBC who have failed BCG treatment. Source of Funding: NIH Intramural Cancer Research Program © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e248 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Genesis Rivera-Marquez More articles by this author Beatriz Walter More articles by this author Rebecca Dolan More articles by this author Sonia Belfield More articles by this author Maria Merino More articles by this author Sandeep Gurram More articles by this author Andrea Apolo More articles by this author Scot Niglio More articles by this author Piyush Agarwal More articles by this author Vladimir A. Valera More articles by this author Expand All Advertisement PDF downloadLoading ...