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
A. James1, P. Mulholland2, S. Peoples3, O. Al-Salihi4, C. Twelves5, S. Jefferies6, S. Halford7, J. Ritchie7, H. Singh-Jasuja8, R. Rampling9
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.