A Cancer Research UK first time in human phase I trial of IMA950 (novel multi peptide therapeutic vaccine) in patients with newly diagnosed glioblastoma

Rampling, R. et al. (2016) A Cancer Research UK first time in human phase I trial of IMA950 (novel multi peptide therapeutic vaccine) in patients with newly diagnosed glioblastoma. Clinical Cancer Research, 22(19), pp. 4776-4785. (doi: 10.1158/1078-0432.CCR-16-0506) (PMID:27225692) (PMCID:PMC5026298)

Abstract

PURPOSE: To perform a two-cohort, phase 1 safety and immunogenicity study of IMA950 in addition to standard chemo-radiotherapy (CRT) and adjuvant temozolomide in patients with newly diagnosed glioblastoma (GBM). IMA950 is a novel GBM specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAPs), identified on human leukocyte antigen (HLA) surface receptors in primary human GBM tissue. EXPERIMENTAL DESIGN: Patients were HLA A*02 positive and had undergone tumor resection. Vaccination comprised 11 intradermal injections with IMA950 plus GM-CSF over a 24 week period, beginning 7-14 days prior to initiation of CRT (Cohort 1) or 7 days post CRT (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), pre-treatment 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 pre-treatment Treg levels on IMA950 immunogenicity was observed and steroids did not affect TUMAP responses. PFS was 74% at 6 months and 31% at 9 months. CONCLUSION: 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.

• Item Type: Articles
• Additional Information: This work was supported by grant C222/A11422 from Cancer Research UK. This work was also managed and sponsored by the Cancer Research UK Centre for Drug Development. Immatics Biotechnologies provided pharmacodynamic assay support and supplied IMA950 for this study.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stewart, Dr William and Rampling, Professor Roy and James, Dr Allan
• Authors: Rampling, R., Peoples, S., Mulholland, P. J., James, A., Al-Salihi, O., Twelves, C. J., McBain, C., Jefferies, S., Jackson, A., Stewart, W., Lindner, J., Kutscher, S., Hilf, N., McGuigan, L., Peters, J., Hill, K., Schoor, O., Singh-Jasuja, H., Halford, S. E., and Ritchie, J. W.A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 25 May 2016
• Copyright Holders: Copyright © 2016 American Association for Cancer Research
• First Published: First published in Clinical Cancer Research 22(19):4776-4785
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher