title: 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.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY. Electronic address: chaftj@mskcc.org.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Chaft
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Anya
authors.initials: A
authors.lastname: Litvak
authors.affiliation: Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Arcila
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Payal
authors.initials: P
authors.lastname: Patel
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: D'Angelo
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.affiliation: GlobeImmune, Inc, Louisville, CO.
authors.forename: Alicia
authors.initials: A
authors.lastname: Mattson
authors.affiliation: GlobeImmune, Inc, Louisville, CO.
authors.forename: Claire
authors.initials: C
authors.lastname: Coeshott
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Bernard
authors.initials: B
authors.lastname: Park
authors.affiliation: GlobeImmune, Inc, Louisville, CO.
authors.forename: David M
authors.initials: DM
authors.lastname: Apelian
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D060830:Consolidation Chemotherapy; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D018631:ras Proteins / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Consolidation; Early-stage; Immunotherapy; Lung cancer