title: A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma.
abstract: OBJECTIVE
  To perform a two-cohort, phase I safety and immunogenicity study of IMA950 in addition to standard chemoradiotherapy and adjuvant temozolomide in patients with newly diagnosed glioblastoma. IMA950 is a novel glioblastoma-specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAP), identified on human leukocyte antigen (HLA) surface receptors in primary human glioblastoma tissue.
  
  
  METHODS
  Patients were HLA-A*02-positive and had undergone tumor resection. Vaccination comprised 11 intradermal injections with IMA950 plus granulocyte macrophage colony-stimulating factor (GM-CSF) over a 24-week period, beginning 7 to 14 days prior to initiation of chemoradiotherapy (Cohort 1) or 7 days after chemoradiotherapy (Cohort 2). Safety was assessed according to NCI CTCAE Version 4.0 and TUMAP-specific T-cell immune responses determined. Secondary observations included progression-free survival (PFS), pretreatment regulatory T cell (Treg) levels, and the effect of steroids on T-cell responses.
  
  
  RESULTS
  Forty-five patients were recruited. Related adverse events included minor injection site reactions, rash, pruritus, fatigue, neutropenia and single cases of allergic reaction, anemia and anaphylaxis. Two patients experienced grade 3 dose-limiting toxicity of fatigue and anaphylaxis. Of 40 evaluable patients, 36 were TUMAP responders and 20 were multi-TUMAP responders, with no important differences between cohorts. No effect of pretreatment Treg levels on IMA950 immunogenicity was observed, and steroids did not affect TUMAP responses. PFS rates were 74% at 6 months and 31% at 9 months.
  
  
  CONCLUSIONS
  IMA950 plus GM-CSF was well-tolerated with the primary immunogenicity endpoint of observing multi-TUMAP responses in at least 30% of patients exceeded. Further development of IMA950 is encouraged. Clin Cancer Res; 22(19); 4776-85. ©2016 AACRSee related commentary by Lowenstein and Castro, p. 4760.
authors.affiliation: University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
authors.forename: Roy
authors.initials: R
authors.lastname: Rampling
authors.affiliation: Edinburgh Centre for Neuro-Oncology, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Sharon
authors.initials: S
authors.lastname: Peoples
authors.affiliation: Department of Oncology, University College London Hospitals, London, United Kingdom.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mulholland
authors.affiliation: University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
authors.forename: Allan
authors.initials: A
authors.lastname: James
authors.affiliation: Adult Neuro-Oncology, Southampton University Hospitals NHS Trust, Southampton, United Kingdom.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Salihi
authors.affiliation: Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Twelves
authors.affiliation: The Christie NHS Foundation Trust, Withington, Manchester, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: McBain
authors.affiliation: Cambridge Cancer Trials Centre, Oncology Clinical Trials, Addensbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jefferies
authors.affiliation: Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Department of Neuropathology, The Queen Elizabeth University Hospital, Glasgow, United Kingdom.
authors.forename: Willie
authors.initials: W
authors.lastname: Stewart
authors.affiliation: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors.forename: Juha
authors.initials: J
authors.lastname: Lindner
authors.affiliation: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kutscher
authors.affiliation: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hilf
authors.affiliation: Cancer Research UK Centre for Drug Development, London, United Kingdom.
authors.forename: Lesley
authors.initials: L
authors.lastname: McGuigan
authors.affiliation: Cancer Research UK Centre for Drug Development, London, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Peters
authors.affiliation: Cancer Research UK Centre for Drug Development, London, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Hill
authors.affiliation: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schoor
authors.affiliation: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Singh-Jasuja
authors.affiliation: Cancer Research UK Centre for Drug Development, London, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Halford
authors.affiliation: Cancer Research UK Centre for Drug Development, London, United Kingdom. james.ritchie@cancer.org.uk.
authors.forename: James W A
authors.initials: JW
authors.lastname: Ritchie
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D019496:Cancer Vaccines / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; C000625803:IMA950; D010455:Peptides