PD34-10 FIRST RESULTS OF NURE-COMBO: a PHASE 2 STUDY OF NEOADJUVANT NIVOLUMAB (NIVO) AND NAB-PACLITAXEL (ABX) FOLLOWED BY POSTSURGICAL ADJUVANT NIVO IN PATIENTS (PTS) WITH MUSCLE-INVASIVE BLADDER CANCER (MIBC)

You have accessJournal of UrologyBladder Cancer: Invasive III (PD34)1 May 2024PD34-10 FIRST RESULTS OF NURE-COMBO: a PHASE 2 STUDY OF NEOADJUVANT NIVOLUMAB (NIVO) AND NAB-PACLITAXEL (ABX) FOLLOWED BY POSTSURGICAL ADJUVANT NIVO IN PATIENTS (PTS) WITH MUSCLE-INVASIVE BLADDER CANCER (MIBC) Andrea Necchi, Chiara Mercinelli, Giuseppe Basile, Daniele Raggi, Antonio Cigliola, Valentina Tateo, Damiano Patanè, Emanuele Crupi, Maurizio Colecchia, Marco Moschini, Giulio Avesani, Giorgio Brembilla, Francesco De Cobelli, Alberto Briganti, Jeffrey Ross, and Francesco Montorsi Andrea NecchiAndrea Necchi , Chiara MercinelliChiara Mercinelli , Giuseppe BasileGiuseppe Basile , Daniele RaggiDaniele Raggi , Antonio CigliolaAntonio Cigliola , Valentina TateoValentina Tateo , Damiano PatanèDamiano Patanè , Emanuele CrupiEmanuele Crupi , Maurizio ColecchiaMaurizio Colecchia , Marco MoschiniMarco Moschini , Giulio AvesaniGiulio Avesani , Giorgio BrembillaGiorgio Brembilla , Francesco De CobelliFrancesco De Cobelli , Alberto BrigantiAlberto Briganti , Jeffrey RossJeffrey Ross , and Francesco MontorsiFrancesco Montorsi View All Author Informationhttps://doi.org/10.1097/01.JU.0001008768.36634.79.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MIBC is a systemic disease with a high risk of recurrence after radical cystectomy (RC), that represents the standard of care (SOC) for cisplatin-ineligible pts. Initial data suggest that ABX is active in combination with pembrolizumab in advanced urothelial carcinoma (UC; PMID:32979512). We report results from a phase 2 trial of NIVO+ABX followed by RC and adjuvant NIVO in pts with MIBC (NCT04876313). METHODS: Eligible pts who were cisplatin unfit or declined cisplatin-based treatment had previously untreated MIBC (clinical stage T2-T4a, N0-1, M0, assessed via CT and MRI scan), Eastern Cooperative Oncology Group performance status ≤1, and predominant (>50%) UC histology. Pts received 4 cycles of NIVO 360 mg Q3W+ABX 125 mg/m2 on Day 1 and 8, Q3W, followed by RC and by 13 administrations of adjuvant NIVO 360 mg Q3W. The primary endpoint was the pathologic complete response rate (ypT0N0). Secondary endpoints were major pathological response (ypT≤1N0), safety (CTCAE v5.0) and event-free survival (EFS). Tumor biomarkers included comprehensive genomic profiling (CGP) and circulating tumor DNA assay (Signatera). RESULTS: 31 pts were enrolled from 12/2021 to 06/2023; 17 (54.8%) had a cT3-4 stage, 14 (45.2%) a cT2, 2 (6.4%) had N1 stage, 15 (48.4%) had a variant histology component. All 31 pts concluded the neoadjuvant treatment and were evaluable for the primary endpoint. A total of 4 pts (12.9%) received <4 cycles of neoadjuvant treatment due to treatment-related adverse events (TRAEs). Four pts had G3 TRAEs, including neutropenia (2), asthenia (1), increased AST/ALT (2), neurotoxicity (1) and acute renal failure (1). Three pts refused RC and were offered reTURBT prior to maintenance NIVO after evidence of ctDNA negative assay and MRI complete response. In total, 12 pts (38.7%; 95% CI 21.8-57.8) achieved an ypT0N0 response and 22 (70.9%; 95% CI 51.9-85.8) an ypT≤1N0 response. No disease progressions (PD) occurred during neoadjuvant treatment. After a median follow-up of 10.6 months (IQR: 8-16), one pt had a PD: 12-month EFS was 96.4% (95% CI: 89.9-100). Mean tumor mutation burden (TMB) was 12.3 mut/Mb for ypT0N0 responders vs 5.8 mut/Mb for non-responders. CONCLUSIONS: The first results from Nure-Combo trial suggest this novel chemo-immunotherapy combination with NIVO+ABX could be an effective and safe perioperative strategy in pts with MIBC with sustained efficacy post-RC. These results could expand the opportunities of chemotherapy combinations beyond cisplatin. Results also strengthen the role of clinical complete response to envision organ-sparing approaches. Source of Funding: AIRC (Associazione Italiana per la Ricerca sul Cancro)Bristol Myers Squibb (BMS) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e722 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Andrea Necchi More articles by this author Chiara Mercinelli More articles by this author Giuseppe Basile More articles by this author Daniele Raggi More articles by this author Antonio Cigliola More articles by this author Valentina Tateo More articles by this author Damiano Patanè More articles by this author Emanuele Crupi More articles by this author Maurizio Colecchia More articles by this author Marco Moschini More articles by this author Giulio Avesani More articles by this author Giorgio Brembilla More articles by this author Francesco De Cobelli More articles by this author Alberto Briganti More articles by this author Jeffrey Ross More articles by this author Francesco Montorsi More articles by this author Expand All Advertisement PDF downloadLoading ...