Format

Send to

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

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.

Author information

1
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.
2
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
3
Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
4
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
5
GlobeImmune, Inc, Louisville, CO.

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.

KEYWORDS:

Consolidation; Early-stage; Immunotherapy; Lung cancer

PMID:
25044103
DOI:
10.1016/j.cllc.2014.06.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center