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Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients.

ABSTRACT: Immunotherapy, including therapeutic vaccines, is increasingly being developed for patients with high-grade glioma, and combinations of immunotherapies and synergy with standard of care are being investigated. In this regard, bevacizumab (BEV) has been shown to synergize with immunotherapy in preclinical studies of glioma and in other tumour entities. Here, we conducted a post-hoc exploratory study to evaluate the effect of the IMA950/poly-ICLC peptide vaccine on subsequent BEV administration in high-grade glioma patients. 16 IMA950-vaccinated and 40 non-vaccinated patients were included. At initial diagnosis, patients benefited from surgery and chemoradiation. At first or subsequent recurrence, patients received 10mg/kg of BEV every 2-3 weeks. Primary endpoints were overall survival (OS) and progression-free survival (PFS) from BEV initiation. IMA950-vaccinated patients did not show improved response to BEV as compared to non-vaccinated patients: there was no difference in median PFS (2.6 vs. 4.2 months for vaccinated and control patients, respectively, p = 0.50) nor in median OS (7.8 vs. 10.0 months for vaccinated and control patients, respectively, p = 0.69). In conclusion, potential synergy of BEV and therapeutic vaccines, when administered sequentially, has yet to be established in the clinical setting of GBM recurrence. Potential synergy of concomitant administration should be tested in future trials.

SUBMITTER: Boydell E

PROVIDER: S-EPMC6520681 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients.

Boydell Emma E Marinari Eliana E Migliorini Denis D Dietrich Pierre-Yves PY Patrikidou Anna A Dutoit Valérie V

Cancers 20190402 4

Immunotherapy, including therapeutic vaccines, is increasingly being developed for patients with high-grade glioma, and combinations of immunotherapies and synergy with standard of care are being investigated. In this regard, bevacizumab (BEV) has been shown to synergize with immunotherapy in preclinical studies of glioma and in other tumour entities. Here, we conducted a post-hoc exploratory study to evaluate the effect of the IMA950/poly-ICLC peptide vaccine on subsequent BEV administration in ...[more]

PMID: 30986995

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Project description:Abstract The IMA950 peptide vaccine is composed of 9 HLA-A2-restricted peptides eluted from the surface of GBM samples and of two HLA class II-binding peptides1. It was tested in combination with poly-ICLC in patients with newly diagnosed GBM, demonstrating safety. The vaccine was able to elicit CD4 and CD8 T cell responses in the peripheral blood in the majority of patients, with however an overall low magnitude of T cell responses and suboptimal migration of elicited T cells to the brain, probably limiting clinical efficacy2,3. With the aim to improve homing of vaccine-specific T cell to the tumor, we are conducting a phase II clinical trial in patients with recurrent GBM testing the IMA950/poly-ICLC multipeptide vaccine with or without the anti-PD1 antibody pembrolizumab (NCT03665545). 24 patients will be included (12 patients in each arm) and pre- and post-vaccination tumor sample will be available, allowing assessing effect of the vaccine at the tumor site. The primary objective of this trial is safety of IMA950/poly-ICLC given together with pembrolizumab. Secondary objectives include (i) estimation of 6, 9 and 12-month progression-free survival (PFS), (ii) overall survival, (iii) analysis of patient quality of life and (iv) of the synergy/immunogenicity of IMA950/poly-ICLC and pembrolizumab. Immunomonitoring will include measure of vaccine-induced immune responses, IHC for immune cell markers, RNA/TCR sequencing and methylome analysis, to assess vaccine-induced T cell responses, immune modulation and potential signatures predictive of response. Thus far, 6 patients have been included (3 in each arm). Preliminary results show CD4 and CD8 T cell responses to the vaccine are detected in both groups in the peripheral blood. Analysis at the tumor site and comparison between arms will be performed once all patients have been included. 1. Dutoit, V. et al. Brain (2012); 2. Migliorini, D. et al. Neuro Oncol (2019); 3. Rampling, R. et al. Clin Cancer Res(2016)

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Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients.

Publications

Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients.

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