623 AI-designed personalized neoantigen vaccine, EVX-02, induces robust T-cell responses in melanoma patients

BackgroundEVX-02, a personalized neoantigen DNA vaccine, was assessed in combination with an anti-PD-1 therapy (nivolumab) in patients with fully resected melanoma and at high risk of disease recurrence. The neoantigen EVX-02 vaccines were designed by Evaxion’s proprietary AI platform, PIONEER, based on the unique mutational profile of each tumor and the patient’s HLA type. PIONEER identifies cancer-specific mutations by analyzing differences in the DNA sequences of a tumor and a healthy sample. The non-synonymous subset of these cancer-specific mutations is then further processed in silico to generate candidate neoantigen sequences. The objectives of this study were to assess safety and tolerability, vaccine neoantigen immunogenicity and relapse-free survival at 12 months after nivolumab initiation.EVX-02 treatment was found to be safe and well-tolerated. A total of 10 patients received all scheduled EVX-02 vaccinations and were relapse-free at their last assessment.MethodsTo monitor EVX-02 induced T-cell responses and to profile soluble serum biomarker levels, blood samples were collected before, during and after EVX-02 treatment.Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples and assessed for T-cell immunogenicity after in vitro stimulation with vaccine neoantigens to facilitate the expansion of neoantigen reactive T cells. The neoantigen-specific T-cell responses were investigated by cytokine release assays, including interferon gamma (IFNy) ELISpot and intracellular cytokine staining (ICS). T-cell reactivity was addressed by stimulating the PBMCs with the collection of neoantigens or single neoantigens.ResultsMeasuring the T-cell responses over time showed that there on average was an increase in magnitude and that the responses were long-lasting. ICS analysis demonstrated that both CD4+ and CD8+ T cells were reactive to the vaccine neoantigens. Analysis of the immunogenic potential of the individual vaccine neoantigens revealed that around 50% of the vaccine neoantigens were immunogenic and although pre-existing immune recognition of vaccine neoantigens was observed, there was a strong increase in the number of immunogenic neoantigens after EVX-02 vaccination. Interestingly, there was a correlation between the PIONEER predicted neoantigen quality and immunogenicity.ConclusionsEVX-02 successfully induced neoantigen-reactive T cells in all patients that received all scheduled EVX-02 vaccinations. The EVX-02 vaccine mobil