Immunogenicity of GI-4000 vaccine in adjuvant consolidation therapy following definitive treatment in patients with stage I-III adenocarcinoma of the lung with G12C, G12D, or G12V KRAS mutations.

Abstract

7070 Background: All patients at MSKCC with lung adenocarcinoma undergo reflex testing for EGFR and KRAS mutations at the time of surgical resection. KRAS mutations occurred in 19% of resected lung adenocarcinomas at MSKCC from 2006- 4/2009. GI-4000 is a recombinant, yeast-based vaccine (S. cerevisiae) engineered to express one of 4 mutated RAS oncoproteins. Methods: GI-4000 was administered as adjuvant therapy to patients with stage I-III lung adenocarcinomas and G12C, G12D, or G12V KRAS mutations after the completion of curative therapies. All patients were disease free at their first post-treatment assessment. GI-4000 was given for 3 weekly doses, 6 monthly doses, then every 3 months for up to 3 years. The primary endpoint was vaccine-induced T cell responses documented by interferon-γ ELISpot assay in peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with RAS peptide pools from the specific mutation present in their tumor. Results: 24 subjects were enrolled. Women=17, Stage IA=10, IB=4, II=2, III=8, median age 67 (range 50-80), G12C=15, G12V=3, G12D=6, median # of doses per subject =9 (range 1-16). To date, there have been no serious adverse events related to GI-4000. 17/24 patients had adequate immune sampling to be analyzed by ELISpot assay, G12V patients (n=3) are still undergoing testing. 8/17 (47%) of the patients developed an immune response to mutant RAS; 5/9 (55%) developed a treatment emergent response and 3/8 (37%) developed an improvement in a pre-existing baseline response based on pre-specified immunologic criteria. Conclusions: MSKCC’s program of reflex testing of lung adenocarcinoma resection specimens permits the identification of patients for KRAS specific therapy. GI-4000 is immunogenic in targeting mutated KRAS as an adjuvant “consolidation” therapy in patients with stage I-III lung adenocarcinomas harboring KRAS mutations. These data warrant further study of GI-4000 in KRAS mutant lung adenocarcinomas and other cancers with these specific mutations.