Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation

Clin Lung Cancer. 2014 Nov;15(6):405-10. doi: 10.1016/j.cllc.2014.06.002. Epub 2014 Jun 21.


Introduction: Patients with early-stage lung cancer have a high risk of recurrence despite multimodality therapy. KRAS-mutant lung adenocarcinomas are the largest genetically defined subgroup, representing 25% of patients. GI-4000 is a heat-killed recombinant Saccharomyces cerevisiae yeast-derived vaccine expressing mutant KRAS proteins. The present phase II study assessed the feasibility, immunogenicity, and safety of the GI-4000 vaccine in patients with early-stage, KRAS-mutant lung cancer.

Materials and methods: Patients with stage I-III KRAS-mutant lung cancer who completed curative therapy were enrolled. The patients received the genotype matched GI-4000 vaccine for ≤ 3 years or until intolerance, disease recurrence, or death. The KRAS antigen T-cell response was assessed using the interferon-gamma enzyme-linked immunospot assay in peripheral blood mononuclear cells. The study was powered to detect an immune response in ≥ 25% of patients.

Results: A total of 24 patients were enrolled over 28 months. No vaccine-related serious adverse events occurred. One patient withdrew consent because of pain at the injection site. The study met its primary endpoint, with 50% of patients developing an immune response to mutant KRAS. The median number of vaccinations received was 15 (range, 1-19). Ten patients experienced disease recurrence, and 6 died. Compared with the genotypically matched historical controls, the recurrence rates were equivalent but overall survival showed a favorable trend.

Conclusion: GI-4000 was well tolerated and immunogenic when used as consolidation therapy in patients with stage I-III KRAS-mutant lung cancer. The patterns of recurrence and death observed in the present study can be used to design a randomized study of GI-4000 with overall survival as the primary endpoint.

Keywords: Consolidation; Early-stage; Immunotherapy; Lung cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Aged
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cells, Cultured
  • Consolidation Chemotherapy
  • Female
  • GTP-Binding Protein alpha Subunits, G12-G13 / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Staging
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / immunology
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • ras Proteins / adverse effects
  • ras Proteins / genetics
  • ras Proteins / immunology
  • ras Proteins / therapeutic use*


  • Cancer Vaccines
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • GTP-Binding Protein alpha Subunits, G12-G13
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins