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IMvigor010, a phase III study of adjuvant atezolizumab vs observation in patients (pts) with muscle-invasive urothelial carcinoma (UC)

By: Gschwend J.1, Bellmunt J.2, Castellano D.3, Daneshmand S.4, Hussain M.5, Nishiyama H.6, Powles T.7, Degaonkar V.8, Nguyen Duc A.9, Culine S.10
Institutes: 1Technical University of Munich, Dept. of Urology, Munich, Germany, 2Bladder Cancer Center, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, United States of America, 3Hospital Universitario 12 De Octubre, Dept. of Oncology, Madrid, Spain, 4University of Southern California, Dept. of Oncology, Los Angeles, United States of America, 5Northwestern University, Dept. of Oncology, Chicago, United States of America, 6University of Tsukuba, Dept. of Oncology, Ibaraki, Japan, 7Barts Cancer Institute, Queen Mary University of London, London, United Kingdom, 8Genentech, Inc., Dept. of Oncology, South San Francisco, United States of America, 9Roche, Dept. of Oncology, Basel, Switzerland, 10Hôpital Saint-Louis, Dept. of Oncology, Paris, France
Introduction & ObjectivesRadical cystectomy (with or without cisplatin-based neoadjuvant chemotherapy [NAC]) is the mainstay treatment for muscle-invasive UC. No standard NAC or adjuvant chemotherapy (AC) exists for muscle-invasive UC pts not eligible for cisplatin-based (N)AC. Atezolizumab (anti–PD-L1), approved in the US for metastatic urothelial carcinoma, is also effective and tolerable in the first-line cisplatin-ineligible setting (Bellmunt, ESMO 2016). Here, we describe the Phase III, open-label, multicenter, randomized, controlled trial IMvigor010 (ClinicalTrials.gov NCT02450331). IMvigor010 is designed to evaluate the efficacy and safety of adjuvant atezolizumab vs observation in pts with muscle-invasive bladder or upper-tract UC (UTUC) who are at high risk of recurrence following cystectomy.Material & MethodsIMvigor010 is enrolling pts with histologically confirmed muscle-invasive UC of the bladder, renal pelvis or ureters. Eligible pts must have an ECOG PS 0-2 and an evaluable sample for PD-L1 immunohistochemical testing (VENTANA SP142 assay). All pts are required to have surgical resection with lymph node dissection (radical cystectomy or nephroureterectomy) and negative surgical margins (except for carcinoma in situ at distal ureteral/urethral margin). For pts who received NAC, tumor staging must be ypT2-4a or ypN+ (ypT2-4 or ypN+ for pts with UTUC). Pts not treated with NAC must also be ineligible for or have declined cisplatin-based AC, with tumors staged at pT3-4a or pN+ (pT3-4 or pN+ for UTUC). Post-surgical AC or radiation are not permitted. For pts with UTUC, post-surgical topical chemotherapy or BCG are not allowed. Enrollment in this study initially required selection based on PD-L1 expression on tumor-infiltrating immune cells (IC) but, following a protocol amendment, is now expanded to pts regardless of PD-L1 status. Pts are randomized 1:1 to observation or atezolizumab (1200 mg IV q3w) as adjuvant treatment for 16 cycles or 1 y (whichever occurs first). The primary efficacy endpoint is disease-free survival. Secondary efficacy endpoints include overall survival, disease-specific survival, distant metastasis–free survival and non–urinary tract recurrence-free survival. Safety, pharmacokinetics and pt-reported outcomes will also be assessed. Exploratory analyses will assess predictive, prognostic and pharmacodynamic biomarkers. Stratification factors include number of lymph nodes resected (< 10 vs ≥ 10), nodal status (positive vs negative), tumor stage after resection (≤ pT2 vs pT3/pT4), PD-L1 status (IC0/1 vs IC2/3) and prior NAC (yes vs no). Investigators will assess disease recurrence based on radiographic evidence and available biopsy results. This trial is currently enrolling globally, with a target of approximately 700 pts. Sponsor: Roche/Genentech. Gschwend J.1, Bellmunt J.2, Castellano D.3, Daneshmand S.4, Hussain M.5, Nishiyama H.6, Powles T.7, Degaonkar V.8, Nguyen Duc A.9, Culine S.10 32nd Annual EAU Congress London 1Technical University of Munich, Dept. of Urology, Munich, Germany, 2Bladder Cancer Center, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, United States of America, 3Hospital Universitario 12 De Octubre, Dept. of Oncology, Madrid, Spain, 4University of Southern California, Dept. of Oncology, Los Angeles, United States of America, 5Northwestern University, Dept. of Oncology, Chicago, United States of America, 6University of Tsukuba, Dept. of Oncology, Ibaraki, Japan, 7Barts Cancer Institute, Queen Mary University of London, London, United Kingdom, 8Genentech, Inc., Dept. of Oncology, South San Francisco, United States of America, 9Roche, Dept. of Oncology, Basel, Switzerland, 10Hôpital Saint-Louis, Dept. of Oncology, Paris, France 70178 AM17-4509 212
  • Type: Abstract
  • Date: 25-03-2017
  • Rating: 0,0
  • Views: 497
  • Event: 32nd Annual EAU Congress London
  • Nr: 212
  • Session: Ongoing prospective trials
  • Location: Saturday, 25 March 2017, 14:15 - 15:45, Room Vienna, North Hall (Level 1)