Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients

Neuro Oncol. 2019 Jul 11;21(7):923-933. doi: 10.1093/neuonc/noz040.


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: NCT01920191.

Keywords: IMA950; glioma; immune response; peptide vaccine; poly-ICLC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / immunology
  • Astrocytoma / pathology
  • Astrocytoma / therapy*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / administration & dosage*
  • Carboxymethylcellulose Sodium / administration & dosage
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Chemoradiotherapy / mortality*
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Glioblastoma / immunology
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Poly I-C / administration & dosage*
  • Polylysine / administration & dosage
  • Polylysine / analogs & derivatives*
  • Prognosis
  • Survival Rate
  • Vaccines, Subunit / administration & dosage*
  • Young Adult


  • Cancer Vaccines
  • IMA950
  • Peptides
  • Vaccines, Subunit
  • Polylysine
  • poly ICLC
  • Carboxymethylcellulose Sodium
  • Poly I-C

Associated data