PD11-11 INTERIM RESULTS FROM PURE-01: A PHASE 2, OPEN-LABEL STUDY OF NEOADJUVANT PEMBROLIZUMAB (PEMBRO) BEFORE RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE UROTHELIAL BLADDER CARCINOMA (MIUC)

Abstract

You have accessJournal of UrologyBladder Cancer: Invasive I1 Apr 2018PD11-11 INTERIM RESULTS FROM PURE-01: A PHASE 2, OPEN-LABEL STUDY OF NEOADJUVANT PEMBROLIZUMAB (PEMBRO) BEFORE RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE UROTHELIAL BLADDER CARCINOMA (MIUC) Andrea Necchi, Alberto Briganti, Daniele Raggi, Patrizia Giannatempo, Marco Bianchi, Luigi Mariani, Antonella Messina, Andrea Anichini, Massimo Freschi, Maurizio Colecchia, Roberto Salvioni, Renzo Colombo, Andrea Gallina, and Francesco Montorsi Andrea NecchiAndrea Necchi More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Daniele RaggiDaniele Raggi More articles by this author , Patrizia GiannatempoPatrizia Giannatempo More articles by this author , Marco BianchiMarco Bianchi More articles by this author , Luigi MarianiLuigi Mariani More articles by this author , Antonella MessinaAntonella Messina More articles by this author , Andrea AnichiniAndrea Anichini More articles by this author , Massimo FreschiMassimo Freschi More articles by this author , Maurizio ColecchiaMaurizio Colecchia More articles by this author , Roberto SalvioniRoberto Salvioni More articles by this author , Renzo ColomboRenzo Colombo More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , and Francesco MontorsiFrancesco Montorsi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.634AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MIUC is an aggressive disease and >40% of patients (pts) will develop recurrence after radical cystectomy (RC). Cisplatin-based neoadjuvant chemotherapy (CT) yields Level 1 evidence, but it is administered in a minority of pts. Pembro is an EMA and FDA-approved therapy for metastatic UC after platinum failure or for cisplatin-ineligible pts. METHODS PURE-01 (NCT02736266) is an open-label, single-arm, phase 2 study to evaluate the activity, medical and surgical safety, and immune modulatory effects of pembro administered before RC. Inclusion criteria: predominant UC histology and </=T3bN0 stage, regardless of eligibility to cisplatin-based CT. Pts received 3 cycles of pembro 200mg 3 weekly before RC. CT scan, FDG-PET/CT scan, and bladder multiparametric MRI (mpMRI) were done during screening and before RC. No additional anti PD-1/PD-L1 therapy was allowed post-operatively. Pathologic complete response (pT0) is the primary endpoint. All pts enrolled who receive at least 1 cycle of study drug will be included in the ITT analysis. The H1 is ypT0 >/=20% and H0 ypT0</=10%. In a 2-stage design, 90 pts overall will be accrued (80% power and a 2-sided alpha at 10%). CTCAE v4.03 will be used to grade adverse events (AE), and immune-related AE (irAE). The associations of an 18-gene expression profile and IHC PD-L1 combined positive score (CPS) with pathologic response will be evaluated. TURB specimens from all pts will be also analyzed with FoundationOne test. A first interim analysis for safety is presented. RESULTS From 02-11/2017, 24 pts were enrolled (22M, 2F). 17 had cT3, 7 cT2, 6 had hydronephrosis. 20 pts are evaluable for safety: 1 pt (5%) had G3 irAE (ALT increase) and suspended pembro; 3 (15%) had reversible G2 irAE. There were 3 IIIa and 1 IIIb complications according to Clavien-Dindo classification. At the time of data analysis, 14 pts are evaluable for the primary endpoint. There were 4/14 ypT0 (28.6%) and 3 ypTa/is (total ypT</=2 rate: 50%). Median n. of removed lymph nodes was 27. 19 pts had MRI-evaluable response: baseline median tumor thickness was 10mm vs 5mm after pembro, coupled with significant mpMRI changes. CONCLUSIONS According to the first presented data on the preoperative use of immune-checkpoint inhibitors before major surgery, pembro was safe and endowed with a potent effect in MIUC. Activity results and full translational findings in the first 20 pts will be presented. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e238 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Andrea Necchi More articles by this author Alberto Briganti More articles by this author Daniele Raggi More articles by this author Patrizia Giannatempo More articles by this author Marco Bianchi More articles by this author Luigi Mariani More articles by this author Antonella Messina More articles by this author Andrea Anichini More articles by this author Massimo Freschi More articles by this author Maurizio Colecchia More articles by this author Roberto Salvioni More articles by this author Renzo Colombo More articles by this author Andrea Gallina More articles by this author Francesco Montorsi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...