Phase I/II Trial Testing Safety and Immunogenicity of the Multipeptide IMA950/poly-ICLC Vaccine in Newly Diagnosed Adult Malignant Astrocytoma Patients

Overview

Journal Neuro Oncol

Publisher Oxford University Press

Specialties Neurology
Oncology

Date 2019 Feb 13

PMID 30753611

Citations 63

Authors

Denis Migliorini

Valerie Dutoit

Mathilde Allard

Nicole Grandjean Hallez

Eliana Marinari

Valerie Widmer

Geraldine Philippin

Francesca Corlazzoli

Robin Gustave

Mario Kreutzfeldt

Nathalie Blazek

Joelle Wasem

Andreas Hottinger

Avinash Koka

Shahan Momjian

Alexander Lobrinus

Doron Merkler

Maria-Isabel Vargas

Paul R Walker

Anna Patrikidou

Pierre-Yves Dietrich

Affiliations

Soon will be listed here.

Abstract

Background: Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose) in human leukocyte antigen A2+ glioma patients.

Methods: Adult patients with newly diagnosed glioblastoma (n = 16) and grade III astrocytoma (n = 3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 major histocompatibility complex [MHC] class I and 2 MHC class II peptides) intradermally and poly-ICLC intramuscularly (i.m.). After protocol amendment, IMA950 and poly-ICLC were mixed and injected subcutaneously (n = 7) or i.m. (n = 6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral cluster of differentiation (CD)4 and CD8 T-cell responses.

Results: The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T-cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained T helper 1 CD4 T-cell responses. For the entire cohort, CD8 T-cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients.

Conclusion: We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients.

Trial Registration: Clinicaltrials.gov NCT01920191.

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