Original Study 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 Jamie E. Chaft, 1 Anya Litvak, 1 Maria E. Arcila, 2 Payal Patel, 1 Sandra P. D’Angelo, 1 Lee M. Krug, 1 Valerie Rusch, 3 Alicia Mattson, 4 Claire Coeshott, 4 Bernard Park, 3 David M. Apelian, 4 Mark G. Kris, 1 Christopher G. Azzoli 1 Abstract This phase II study evaluated the feasibility, immunogenicity, and safety of GI-4000, a yeast derived vaccine expressing mutant KRAS (Kirsten rat sarcoma viral oncogene homolog) proteins, in patients with early stage KRAS mutant lung cancers who completed curative therapy. Twenty-four patients received the genotype matched GI-4000 vaccine for £ 3 years or until disease recurrence or intolerance. GI-4000 was found to be well tolerated and immunogenic when used as consolidation therapy in patients with stage I-III KRAS mutant lung cancers. 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 yeastederived 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. Clinical Lung Cancer, Vol. 15, No. 6, 405-10 ª 2014 Elsevier Inc. All rights reserved. Keywords: Consolidation, Early-stage, Immunotherapy, Lung cancer 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 2 Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan- Kettering Cancer Center, New York, NY 3 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 4 GlobeImmune, Inc, Louisville, CO Submitted: Apr 14, 2014; Revised: May 30, 2014; Accepted: Jun 17, 2014; Epub: Jun 21, 2014 Address for correspondence: Jamie E. Chaft, MD, Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065 E-mail contact: chaftj@mskcc.org 1525-7304/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cllc.2014.06.002 Clinical Lung Cancer November 2014 - 405