title: Open-label, multicentre expansion cohort to evaluate imgatuzumab in pre-treated patients with KRAS-mutant advanced colorectal carcinoma.
abstract: OBJECTIVE
  Imgatuzumab (GA201) is a novel anti-epidermal growth factor receptor (anti-EGFR) antibody glycoengineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the efficacy of imgatuzumab in patients with EGFR-positive, KRAS-mutant advanced colorectal cancer.
  
  
  METHODS
  Patients received single-agent imgatuzumab (1400mg on day 1 and 8 followed by q2W) as third line therapy in an open-label, multicentre, non-randomised, expansion study. The primary end-point was tumour response. Pre- and on-treatment biopsies and blood samples were investigated for biomarkers related to imgatuzumab's believed mechanism of action (MoA).
  
  
  RESULTS
  25 patients were treated and the best overall response was stable disease occurring in 40% of patients at 8weeks, 24% at 16weeks and 8% (two patients) at 32weeks. Median overall survival was 9.3months (95% confidence interval (CI): 5.1-12.3). Treatment-related rash, hypomagnesaemia and infusion-related reactions were the most common adverse events. Comparison of pre- and post-treatment biopsies revealed that the number of tumour-infiltrating immune cells increased notably after one cycle of therapy (median compound immune reactive score of 1491 versus 898 cells/mm(3) at baseline), whereas the number of peripheral natural killer cells decreased. A potential association between baseline tumour immune infiltration and clinical efficacy was seen.
  
  
  CONCLUSIONS
  These data may suggest that the MoA of imgatuzumab involves ADCC-related immune effects in the tumour and is not limited to simple receptor blockade.
authors.affiliation: Institut Claudius Regaud and Toulouse III University, Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Delord
authors.affiliation: Vall d'Hebron University Hospital, VHIO, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Oncology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS) [Universidad de Sevilla, CSIC, HUVR], Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Carbonero
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA, University of Valencia, Spain.
authors.forename: Andres
authors.initials: A
authors.lastname: Cervantes
authors.affiliation: Institut Gustave Roussy, Villejuif, France; University Paris South, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez-Roca
authors.affiliation: Institut Claudius Regaud and Toulouse III University, Toulouse, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Bergé
authors.affiliation: Vall d'Hebron University Hospital, VHIO, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.affiliation: Oncology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS) [Universidad de Sevilla, CSIC, HUVR], Seville, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA, University of Valencia, Spain.
authors.forename: Desamparados
authors.initials: D
authors.lastname: Roda
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Delmar
authors.affiliation: Department of Haematological Medicine, King's College, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Oppenheim
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Sophia Soehrman
authors.initials: SS
authors.lastname: Brossard
authors.affiliation: Department of Haematological Medicine, King's College, London, UK.
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
authors.affiliation: Roche Glycart AG, Schlieren, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Manenti
authors.affiliation: Roche Glycart AG, Schlieren, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Passioukov
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Marion Gabriele
authors.initials: MG
authors.lastname: Ott
authors.affiliation: Institut Gustave Roussy, Villejuif, France; University Paris South, France. Electronic address: Jean-Charles.Soria@igr.fr.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D006023:Glycoproteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; C569293:imgatuzumab
keywords: Antibody-dependent cell cytotoxicity; Colorectal neoplasms; Epidermal growth factor; GA201; Human; KRAS protein; RG7160; Receptor