PMID- 27225692 OWN - NLM STAT- MEDLINE DCOM- 20180105 LR - 20240210 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 22 IP - 19 DP - 2016 Oct 1 TI - A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma. PG - 4776-4785 AB - PURPOSE: 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. EXPERIMENTAL DESIGN: 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 (T(reg)) 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. (c)2016 AACRSee related commentary by Lowenstein and Castro, p. 4760. CI - (c)2016 American Association for Cancer Research. FAU - Rampling, Roy AU - Rampling R AD - University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. FAU - Peoples, Sharon AU - Peoples S AD - Edinburgh Centre for Neuro-Oncology, Western General Hospital, Edinburgh, United Kingdom. FAU - Mulholland, Paul J AU - Mulholland PJ AD - Department of Oncology, University College London Hospitals, London, United Kingdom. FAU - James, Allan AU - James A AD - University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. FAU - Al-Salihi, Omar AU - Al-Salihi O AD - Adult Neuro-Oncology, Southampton University Hospitals NHS Trust, Southampton, United Kingdom. FAU - Twelves, Christopher J AU - Twelves CJ AD - Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, United Kingdom. FAU - McBain, Catherine AU - McBain C AD - The Christie NHS Foundation Trust, Withington, Manchester, United Kingdom. FAU - Jefferies, Sarah AU - Jefferies S AD - Cambridge Cancer Trials Centre, Oncology Clinical Trials, Addensbrooke's Hospital, Cambridge, United Kingdom. FAU - Jackson, Alan AU - Jackson A AD - Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom. FAU - Stewart, Willie AU - Stewart W AD - Department of Neuropathology, The Queen Elizabeth University Hospital, Glasgow, United Kingdom. FAU - Lindner, Juha AU - Lindner J AD - Immatics Biotechnologies GmbH, Tubingen, Germany. FAU - Kutscher, Sarah AU - Kutscher S AD - Immatics Biotechnologies GmbH, Tubingen, Germany. FAU - Hilf, Norbert AU - Hilf N AD - Immatics Biotechnologies GmbH, Tubingen, Germany. FAU - McGuigan, Lesley AU - McGuigan L AD - Cancer Research UK Centre for Drug Development, London, United Kingdom. FAU - Peters, Jane AU - Peters J AD - Cancer Research UK Centre for Drug Development, London, United Kingdom. FAU - Hill, Karen AU - Hill K AD - Cancer Research UK Centre for Drug Development, London, United Kingdom. FAU - Schoor, Oliver AU - Schoor O AD - Immatics Biotechnologies GmbH, Tubingen, Germany. FAU - Singh-Jasuja, Harpreet AU - Singh-Jasuja H AD - Immatics Biotechnologies GmbH, Tubingen, Germany. FAU - Halford, Sarah E AU - Halford SE AD - Cancer Research UK Centre for Drug Development, London, United Kingdom. FAU - Ritchie, James W A AU - Ritchie JW AD - Cancer Research UK Centre for Drug Development, London, United Kingdom. james.ritchie@cancer.org.uk. LA - eng GR - 16465/CRUK_/Cancer Research UK/United Kingdom GR - 18097/CRUK_/Cancer Research UK/United Kingdom PT - Clinical Trial, Phase I PT - Journal Article DEP - 20160525 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antigens, Neoplasm) RN - 0 (Antineoplastic Agents) RN - 0 (Cancer Vaccines) RN - 0 (IMA950) RN - 0 (Peptides) SB - IM CIN - Clin Cancer Res. 2016 Oct 1;22(19):4760-4762. PMID: 27521444 MH - Adult MH - Aged MH - Antigens, Neoplasm/immunology/therapeutic use MH - Antineoplastic Agents/therapeutic use MH - Brain Neoplasms/*drug therapy/mortality MH - Cancer Vaccines/*therapeutic use MH - Chemoradiotherapy/methods MH - Disease-Free Survival MH - Female MH - Glioblastoma/*drug therapy/mortality MH - Humans MH - Kaplan-Meier Estimate MH - Lymphocyte Activation/drug effects MH - Male MH - Middle Aged MH - Peptides/*therapeutic use MH - T-Lymphocytes/drug effects MH - United Kingdom MH - Young Adult PMC - PMC5026298 MID - EMS68694 COIS- Statement: Norbert Hilf, Sarah Kutscher, Juha Lindner, Oliver Schoor and Harpreet Singh are current or past employees of Immatics Biotechnologies. Sarah Kutscher, Norbert Hilf, Oliver Schoor and Harpreet Singh have stock ownership interests in Immatics Biotechnologies. Sarah Kutscher, Norbert Hilf, Oliver Schoor, Harpreet Singh have intellectual property interests in Immatics Biotechnologies. Sarah Kutscher, Norbert Hilf, Oliver Schoor and Harpreet Singh have received either travel, accommodation or other expenses from Immatics Biotechnologies during the previous two years. Harpreet Singh has a leadership role at Immatics Biotechnologies. Other authors disclosed no conflicts of interest. EDAT- 2016/05/27 06:00 MHDA- 2018/01/06 06:00 PMCR- 2017/04/01 CRDT- 2016/05/27 06:00 PHST- 2016/02/24 00:00 [received] PHST- 2016/05/11 00:00 [accepted] PHST- 2016/05/27 06:00 [pubmed] PHST- 2018/01/06 06:00 [medline] PHST- 2016/05/27 06:00 [entrez] PHST- 2017/04/01 00:00 [pmc-release] AID - 1078-0432.CCR-16-0506 [pii] AID - 10.1158/1078-0432.CCR-16-0506 [doi] PST - ppublish SO - Clin Cancer Res. 2016 Oct 1;22(19):4776-4785. doi: 10.1158/1078-0432.CCR-16-0506. Epub 2016 May 25.