Background: Tumor-specific neoantigens provide individualized targets for immunotherapy. In silico selection methods are sub-optimal at predicting immunogenic targets, missing up to 70% of true neoantigens. ATLAS is a powerful tool that screens all candidate neoantigens for pre-existing patient-specific CD4 or CD8 responses in an HLA agnostic assessment. ATLAS also identifies inhibitory peptides that may suppress tumor immunity and accelerate tumor progression. The GEN-009 vaccine contains stimulatory but no inhibitory peptide antigens. Methods: GEN-009-101 is a first-in-human phase 1/2a study testing platform feasibility, safety, immunogenicity and clinical activity in selected solid tumors. After next-generation tumor sequencing and cytokine-based ATLAS assessment using autologous T cells and APCs, up to 20 stimulatory synthetic long peptides are used in each personalized vaccine. GEN-009 is administered with poly-ICLC on weeks 0, 3, 6, 12 and 24. Part A, a safety and immunogenicity pilot, has completed target enrollment of patients without evidence of disease to receive GEN-009; Part B has 5 tumor-specific cohorts of up to 15 pts naïve to PD-1 blockade who will receive GEN-009 with a SOC immunotherapy; Part C: up to 15 pts refractory to PD-1 inhibitors will receive GEN-009 monotherapy. Results: GEN-009 has been successfully generated for patients. Repeated dosing has been well tolerated with mild local discomfort and no DLT. ATLAS screening results below show notable interpatient variability; one subject had only CD4 neoantigens, one had only CD8, another had a strong CD8 bias, and one patient had prominent inhibitory peptides. Conclusions: GEN-009 is a neoantigen vaccine that personalizes tumor specific targets and the individual patient’s capacity to respond. Immunogenicity data will assess CD4 and CD8 T cell responses to each vaccine neoantigen. Clinical trial information: NCT03633110