436TiP_PR - Updated results from a Cancer Research UK first in man Phase I trial of IMA950 (a novel multi peptide vaccine) plus GM-CSF in patients with newly di...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Cancer Immunology and Immunotherapy
Central Nervous System Malignancies
Presenter Allan James
Authors A. James1, P. Mulholland2, S. Peoples3, O. Al-Salihi4, C. Twelves5, S. Jefferies6, S. Halford7, J. Ritchie7, H. Singh-Jasuja8, R. Rampling9
  • 1Beatson West of Scotland Cancer Centre, Glasgow/UK
  • 2Dept Of Pathology, UCL Cancer Institute, WC1E 6BT - London/UK
  • 3Centre For Neurooncology, Western General Hospital, EH4 2XU - Edinburgh/UK
  • 4Paediatric/tya/sarcoma Radiotherapy And Adult Neuro-oncology, Southampton University Hospitals NHS Trust, SO16 6YD - Southampton/UK
  • 5Leeds Institute Of Molecular Medicine & St James’s Institute Of Oncology, St James’s University Hospital, LS9 7TF - Leeds/UK
  • 6Dept Of Oncology, Addenbrooke's Hospital, CB2 0QQ - Cambridge/UK
  • 7Drug Development Office, Cancer Research UK, EC1V 4AD - London/UK
  • 8Research And Development, Immatics Biotechnologies, Tuebingen/DE
  • 9Department Of Clinical Oncology, Glasgow University, Glasgow/UK

Abstract

Background: IMA950 is a novel multi-peptide glioblastoma (GBM) specific vaccine that contains 11 HLA-binding tumour-associated peptides (TUMAPs), identified on human leukocyte antigen (HLA) surface receptors in primary human GBM tissue, and one viral (HBV) marker peptide. The TUMAPs are designed to activate TUMAP-specific CD8+ cytotoxic and CD4+ helper T lymphocytes, which then recognise cognate TUMAPs presented by GBM tumour cells and effect a targeted immune response. Methods: Patients (pts) must be eligible for standard treatment of newly diagnosed GBM (maximal safe tumour resection, concomitant chemoradiotherapy (CRT) and adjuvant temozolomide (TMZ)) and be HLA-A*02 positive with no history of autoimmune disease. Vaccination comprises IMA950 plus GM-CSF injected intradermally at 11 time points over a 24 week period. Up to 45 pts will be entered into one of two cohorts with similar schedules. In Cohort 1 vaccination begins 7 to 14 days prior to initial CRT; in Cohort 2 it begins at least 7 days post CRT and 28 days prior to adjuvant TMZ. Safety is assessed according to NCI CTCAE Version 4.0. Immune response is determined by HLA-multimer analysis of vaccine-induced T-cell response in PBMC samples. Secondary objectives include observation of any anti-tumour effects, measurement of pre-treatment regulatory T-cell levels and evaluation of the effect of steroid dose on observed T-cell responses. Results: As of 21-May-12, 25 pts (12 in Cohort 1 and 13 in Cohort 2) have been recruited. Adverse events related to either IMA950 or GM-CSF have been restricted to minor injection site reactions, a single distant allergic rash and a case of isolated asymptomatic neutropenia. Eleven pts have been analysed for immune response with 10 being evaluable (6 from Cohort 1 and 4 from Cohort 2). Eight pts responded to the HBV marker peptide, 8 pts to at least one TUMAP and 4 pts to multiple TUMAPs; 100% of pts in Cohort 2 responded to at least one TUMAP and 50% to multiple TUMAPs. Conclusion: IMA950 plus GM-CSF given alongside standard treatment for GBM has been well tolerated to date and these results already give encouragement for further development of this vaccine.