Virtual Library
Start Your Search
C. Coeshott
Author of
-
+
MO08 - NSCLC - Early Stage (ID 117)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:K. Nakagawa, J. Douillard
- Coordinates: 10/28/2013, 16:15 - 17:45, Bayside Gallery B, Level 1
-
+
MO08.04 - Phase 2 study of the GI-4000 KRAS vaccine following curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, G12V or G12R mutation (ID 2451)
16:30 - 16:35 | Author(s): C. Coeshott
- Abstract
- Presentation
Background
Most patients with early-stage lung cancer will die of recurrent disease despite multimodality therapy with curative intent. KRAS is the most commonly mutated oncogene in lung adenocarcinomas, and patients with resected disease are a unique population amenable to a personalized clinical trial approach. GI4000 is a vaccine created from whole, heat killed recombinant Saccharomyces cerevisiae yeast, overexpressing KRAS Q61L plus Q61(R or H) and either a G12C, G12D, G12V, or G12R mutation. This study aimed to assess the feasibility and immunogenicity of the GI4000 vaccine in patients with KRAS-mutant lung cancers and to compare the outcomes of patients to matched controls.Methods
Patients with Stage I-III KRAS-mutant lung cancers who completed curative therapy were enrolled. Each patient was routinely administered the genotype-matched vaccine from the GI4000 series subcutaneously starting 1-4 months after standard treatment completion: weekly x 3, monthly x 6 and every 3 months for a total of 3 years (19 doses). KRAS-antigen T-cell response was assessed by interferon-γ ELISpot assay in peripheral blood mononuclear cells. The study was powered to detect an immune response rate of ≥25% (N=24 patients). A comparison group matched for age, sex, KRAS genotype and stage was used to compare recurrence and survival using the Kaplan-Meier method with a hazard ratio for survival adjusted for age, sex and stage.Results
In 28 months, 33 patients were screened and 24 patients enrolled. The study met its primary endpoint with 63% of evaluable patients (50% of all patients) developing an antigen-specific immune response. 19 patients had evaluable baseline samples, 9/13 with a negative response at baseline developed a treatment emergent response and 3/6 with a pre-existing baseline response had an increased response over baseline that met pre-specified immunologic criteria. There were no treatment-related Grade 3/4 or severe AEs. The median number of vaccinations received was 15 (range 1-19). 1 patient withdrew consent due to local injection site reaction and 2 died of recurrent disease during study. The baseline characteristics and clinical outcomes of the trial patients and a group of matched controls is presented in the Table below.GI4000 vs. Matched controls GI4000 N=24 N(%) Matched controls N=64 N(%) Stage I II III _____ 12 (50) 5 (21) 7 (29) _____ 42 (66) 2 (3) 20 (31) Age at diagnosis (median) 63 66 Sex Male Female _____ 7 (29) 17 (71) _____ 21 (33) 43 (67) Recurrence free survival per year 1 2 3 _____ 86% 68% 60% _____ 85% 71% 69% Overall survival per year 1 2 3 _____ 100% 100% 92% _____ 93% 88% 83% Hazard ratio for survival (p-value) 0.58 (0.29) Conclusion
The GI4000 vaccine is safe, feasible and immunogenic after completion of curative-intent therapy in patients with KRAS-mutant lung cancers. Recurrence rates are equivalent but overall survival trends favorably when compared to matched controls. Exploratory analysis of survival in the immune responders versus matched controls is underway. A randomized study with prospective biomarker analyses is warranted.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
