A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Abstract

Statement of Translational RelevanceSurvival rates for patients with glioblastoma (GBM) are abysmal, with median overall survival of approximately 15 months. Immunotherapy of GBM is a promising area of investigation, although challenges around identification of novel and immunogenic target antigens exist. IMA950 is a GBM specific vaccine comprising 11 tumor-associated peptides (TUMAPs) developed to address this challenge. We have performed a phase 1 safety and immunogenicity study in newly diagnosed GBM patients using IMA950 plus GM-CSF alongside standard of care chemo-radiotherapy. Our results demonstrate that IMA950 is well tolerated with 90% of patients having a CD8+ T-cell immune response to at least one TUMAP, with 50% responding to two or more TUMAPs. No effect of pre-treatment regulatory T-cell levels on IMA950 immunogenicity was found and steroids did not appear to affect immune responses to the TUMAPs. This data provides evidence to support further development and optimization of IMA950 together with other immunotherapies for GBM. 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.

Tenascin-C at a glance

“…As tenascin-C is a neoantigen in cancer and rheumatoid arthritis, there is scope to profile serum antibodies that recognize tenascin-C (Mock et al, 2015;Schwenzer et al, 2015) and to exploit tenascin-C as an antigen for immunization. Indeed, amongst 11 highly immunogenic peptides that have been delivered within an immunization cocktail to glioblastoma patients (clinical trial phase I), one represented tenascin-C (Dutoit et al, 2012;Rampling et al, 2016). Moreover, aptamers and antibodies that specifically bind to tenascin-C were applied to deliver drugs or immune stimulatory chemokines, such as IL2, into the tumor microenvironment of patients with different cancers (Catania et al, 2015;Gutbrodt et al, 2013 ; reviewed in Spenle et al, 2015b).…”

Unraveling the role of preexisting immunity in prostate cancer patients vaccinated with a HER-2/neu hybrid peptide

“…Local reactions at different vaccinations cycles have been recently correlated with improved clinical outcome [30, 31]. Here, we propose for the first time LR1, i.e.…”

“…Given the amount of the peptide along with the presence of the immunoadjuvant, we considered LR as a more appropriate method to evaluate HER2 preexisting immunity, compared to the standard DTH reaction (100 μg AE36 without GM-CSF). Beside this, it has been previously described that local reaction to the vaccination site can be used to evaluate immune responses in the context of immunomonitoring [30, 31]. Therefore, in the present study LR data represent measurements of induration presented as the orthogonal mean (mm) of the two sites of vaccine inoculation.…”

Engineering challenges for brain tumor immunotherapy

“…A Phase I trial of IMA950 reported an overall survival of 13.2 months with no injection site reaction vs. 26.7 months with an injection site reaction, however, the median age of the injection site reaction groups was significantly lower [93]. …”