1057PD - Final 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 dia...

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Immunotherapy
Central Nervous System Malignancies
Therapy
Presenter Sarah Halford
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors S. Halford1, R. Rampling2, A. James3, S. Peoples4, P. Mulholland5, O. Al-Salihi6, C. Twelves7, C. McBain8, S. Jefferies9, S. Kutscher10, N. Hilf10, L. McGuigan1, J. Peters1, K. Roberts1, O. Schoor10, J. Ritchie1, H. Singh-Jasuja10
  • 1Drug Development Office, Cancer Research UK, EC1V 4AD - London/GB
  • 2Department Of Clinical Oncology, Glasgow University, Glasgow/GB
  • 3Neurooncology, Beatson West of Scotland Cancer Centre, Glasgow/GB
  • 4Centre For Neurooncology, Western General Hospital, EH4 2XU - Edinburgh/GB
  • 5Dept Of Pathology, UCL Cancer Institute, WC1E 6BT - London/GB
  • 6Wessex Neuro-oncology Mdt, Southampton University Hospitals NHS Trust, SO16 6YD - Southampton/GB
  • 7Clinical Cancer Research Groups, Leeds Institute of Molecular Medicine and St James’s Institute of Oncology, Leeds/GB
  • 8Neurooncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 9Dept Of Oncology, Addenbrooke's Hospital, CB2 0QQ - Cambridge/GB
  • 10Research And Development, Immatics Biotechnologies, Tuebingen/DE

 

Abstract

Aim

To determine the safety and immunogenicity of IMA950, a novel multi-peptide glioblastoma (GBM) specific therapeutic vaccine that contains 11 HLA-binding tumour-associated peptides (TUMAPs), identified on human leukocyte antigen (HLA) surface receptors in primary human GBM tissue.

Methods

Patients (pts) were eligible for standard therapy and HLA-A*02 positive. Vaccination comprised 11 intradermal IMA950 plus GM-CSF injections over a 24 week period, beginning 7-14 days prior to initial chemoradiotherapy (CRT) in Cohort 1 or at least 7 days post CRT and 28 days prior to adjuvant temozolomide in Cohort 2. Safety was assessed according to NCI CTCAE Version 4.0 and immune responses determined by HLA-multimer analysis of vaccine-induced T-cell response in PBMCs. Secondary objectives included observation of progression-free survival (PFS), measurement of pre-treatment regulatory T-cell (Treg) levels and evaluation of the effect of steroids on T-cell responses.

Results

Forty five pts were recruited and all were evaluable for safety. Related adverse events included minor injection site reactions (26 pts), rash (5 pts), pruritus (4 pts), fatigue (3 pts), neutropenia (2 pts) and single cases of allergic reaction, anaemia and anaphylaxis. Two pts experienced a dose limiting toxicity of G3 fatigue and G3 anaphylaxis. Of 40 evaluable patients 36 (90%) were TUMAP responders, and 20 (50%) were multi-TUMAP responders with no important differences between the cohorts. No clear effect of pre-treatment Treg levels on IMA950 immunogenicity was observed and no differences in TUMAP responses were noted between pts who were and were not receiving concomitant steroid treatment. PFS was 74% at 6 months and 31% at 9 months. Survival data continues to be collected, with a current median overall survival of 15 months and 11 patients reported to be alive as of 01-May-14.

Conclusions

IMA950 plus GM-CSF given alongside standard treatment for GBM was well tolerated with the primary immunogenicity success endpoint of observing multi-TUMAP responses in at least 30% of patients being exceeded. Further development of IMA950 is therefore encouraged.

Disclosure

S. Kutscher, N. Hilf and O. Schoor: is an employee of Immatics Biotechnologies; H. Singh-Jasuja: is a stock holder and employee of Immatics Biotechnologies. All other authors have declared no conflicts of interest.