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

Research output: Contribution to journalArticle

  • External authors:
  • Roy Rampling
  • Sharon Peoples
  • Paul J Mulholland
  • Allan James
  • Omar Al-Salihi
  • Christopher J Twelves
  • Catherine McBain
  • Sarah Jefferies
  • Willie Stewart
  • Juha Lindner
  • Sarah Kutscher
  • Norbert Hilf
  • Lesley McGuigan
  • Jane Peters
  • Karen Hill
  • Oliver Schoor
  • Harpreet Singh-Jasuja
  • Sarah E Halford
  • James W A Ritchie

Abstract

PURPOSE: To perform a two-cohort, phase I safety and immunogenicity study of IMA950 in addition to standard chemoradiotherapy and adjuvant temozolomide in patients with newly diagnosed glioblastoma. IMA950 is a novel glioblastoma-specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAP), identified on human leukocyte antigen (HLA) surface receptors in primary human glioblastoma tissue.

EXPERIMENTAL DESIGN: Patients were HLA-A*02-positive and had undergone tumor resection. Vaccination comprised 11 intradermal injections with IMA950 plus granulocyte macrophage colony-stimulating factor (GM-CSF) over a 24-week period, beginning 7 to 14 days prior to initiation of chemoradiotherapy (Cohort 1) or 7 days after chemoradiotherapy (Cohort 2). Safety was assessed according to NCI CTCAE Version 4.0 and TUMAP-specific T-cell immune responses determined. Secondary observations included progression-free survival (PFS), pretreatment regulatory T cell (Treg) levels, and the effect of steroids on T-cell responses.

RESULTS: Forty-five patients were recruited. Related adverse events included minor injection site reactions, rash, pruritus, fatigue, neutropenia and single cases of allergic reaction, anemia and anaphylaxis. Two patients experienced grade 3 dose-limiting toxicity of fatigue and anaphylaxis. Of 40 evaluable patients, 36 were TUMAP responders and 20 were multi-TUMAP responders, with no important differences between cohorts. No effect of pretreatment Treg levels on IMA950 immunogenicity was observed, and steroids did not affect TUMAP responses. PFS rates were 74% at 6 months and 31% at 9 months.

CONCLUSIONS: 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. Clin Cancer Res; 22(19); 4776-85. ©2016 AACRSee related commentary by Lowenstein and Castro, p. 4760.

Bibliographical metadata

Original languageEnglish
Pages (from-to)4776-4785
Number of pages10
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Volume22
Issue number19
DOIs
Publication statusPublished - 1 Oct 2016