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 Journal Article
| 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. |
| Article 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: | 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: | adult; cancer chemotherapy; cancer survival; clinical article; controlled study; protein expression; treatment outcome; aged; cancer surgery; unclassified drug; gene mutation; human cell; overall survival; drug tolerability; fatigue; cancer recurrence; cancer growth; drug safety; drug withdrawal; multimodality cancer therapy; cancer radiotherapy; comparative study; cancer staging; recurrence risk; t lymphocyte; controlled clinical trial; drug eruption; phase 2 clinical trial; genotype; lung cancer; in vitro study; cancer therapy; cancer mortality; fever; injection site reaction; pruritus; survival time; lung adenocarcinoma; feasibility study; immune response; immunotherapy; gamma interferon; cancer vaccine; antigen specificity; immunogenicity; antigen recognition; cancer immunization; vaccination; muscle weakness; peripheral edema; lung carcinoma; injection site pain; open study; k ras protein; dry skin; treatment withdrawal; peripheral blood mononuclear cell; early-stage; consolidation; human; male; female; article; gi 4000 vaccine |
| Journal Title: | Clinical Lung Cancer |
| Volume: | 15 |
| Issue: | 6 |
| ISSN: | 1525-7304 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2014-11-01 |
| Start Page: | 405 |
| End Page: | 410 |
| Language: | English |
| DOI: | 10.1016/j.cllc.2014.06.002 |
| PROVIDER: | scopus |
| PUBMED: | 25044103 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
