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Cited by 78Lung Cancer Treatments and MutationsImmunotherapy and Immune ResponsesLung Cancer Research Studies

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

Chaft, Jamie E., Litvak, Anya, Arcila, Maria E., Patel, Payal, D'Angelo, Sandra P., Krug, Lee M., Rusch, Valerie, Mattson, Alicia +5 more·2014·Clinical Lung Cancer
DOI 10.1016/j.cllc.2014.06.002
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Abstract

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.

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  • Vaccination can train the immune system to attack cells expressing mutant KRAS.

    “Vaccination can train the immune system to attack cells expressing mutant KRAS.”

    From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [79]

  • These vaccines are designed to induce antigen-presenting cells to display mutant KRAS, stimulating attacks by cytotoxic T-cells against cancer cells expressing mutant KRAS neoantigen.

    “These vaccines are designed to induce antigen-presenting cells to display mutant KRAS, stimulating attacks by cytotoxic T-cells against cancer cells expressing mutant KRAS neoantigen [78,79,80].”

    From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [79]

  • Chaft et al. revealed a clinical benefit in a patient with KRAS (G12D) metastatic CRC following the adoptive transfer of KRAS (G12D)-specific T cells restricted to HLA-C*08:02.

    “Chaft et al. revealed a clinical benefit in a patient with KRAS (G12D) metastatic CRC following the adoptive transfer of KRAS (G12D)-specific T cells restricted to HLA-C*08:02 [92].”

    From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [92]

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Authors
Chaft, J. E., Litvak, A., Arcila, M. E., Patel, P., D'Angelo, S. P., Krug, L. M., Rusch, V., Mattson, A., Coeshott, C., Park, B., Apelian, D. M., Kris, M. G., & Azzoli, C. G.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • GlobeImmune (United States) (US)
Corresponding author
Chaft, Jamie E.
ORCID
Venue
Clinical Lung Cancer
Publisher
Elsevier BV
Published
2014-11
Volume
15
Issue
6
Pages
405-410
ISSN
1525-7304 (ISSN-L)
DOI
10.1016/j.cllc.2014.06.002
OpenAlex
W2168213782
Cited by
78
References
17
Citations by year
2026: 3 · 2025: 9 · 2024: 5 · 2023: 3 · 2022: 11 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 2 · 2013: 1
FWCI
5.34
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Clinical Lung Cancer (publishedVersion)
  • PubMed (publishedVersion)
Funders
Marty's Fund/Stand Up
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
KRAS-mutant lung adenocarcinoma, recombinant yeast vaccine, KRAS G12C mutation, KRAS G12D mutation, KRAS G12V mutation, vaccine immunogenicity, T cell response, vaccine safety, consolidation therapy, recurrence, overall survival, early-stage lung cancer
MeSH terms
Adenocarcinoma, Aged, Cells, Cultured, Female, Humans, Lung Neoplasms, Lymphocyte Activation, Male, Middle Aged, Mutation, Neoplasm Staging, Proto-Oncogene Proteins, Saccharomyces cerevisiae, T-Lymphocytes, Proto-Oncogene Proteins p21(ras), Treatment Outcome, ras Proteins, Cancer Vaccines, GTP-Binding Protein alpha Subunits, G12-G13, Consolidation Chemotherapy

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