1178PDA phase I trial of GEN-009, a neoantigen vaccine using ATLAS™, an autologous immune assay, to identify immunogenic and inhibitory tumour mutations

Abstract Background Tumor-specific neoantigens provide personalized targets for immunotherapy. Vaccines against epitopes predicted by in silico approaches very rarely induce CD4+ and CD8+ ex vivo T cell responses regardless of formulation. ATLAS selects neoantigens for vaccine inclusion using ex vivo screening of all patient-specific mutations to identify pre-existing CD4+ or CD8+ T cell responses and to exclude inhibitory peptides that suppress immunity and accelerate tumor progression. Preliminary data suggest that the inhibitory peptide profile may predict tumor response to immunotherapy. Methods GEN-009-101 is a phase I/IIa study testing safety, immunogenicity and clinical activity in immune responsive tumors. After next-generation tumor sequencing and ATLAS testing of autologous leukocytes, up to 20 stimulatory synthetic long peptides adjuvanted with poly-ICLC make each personalized vaccine. The immunogenicity pilot has enrolled 9 patients in remission to receive GEN-009 monotherapy. Results 4 patients have participated to the primary immunogenicity readout at day 50 (some data pending). The 17 doses given across patients have induced only mild local discomfort and no DLT. ATLAS results show high interpatient variability. Vaccination has generated immune responses against 94% of administered peptides, and both CD8+ and CD4+ responses in a 44 hr ex vivo fluorospot assay. Ten-day in vitro stimulation (IVS) assays result in broader immune responses. Table:1178PDPTTumor TypeSomatic Mutations/MbATLAS NeoantigensPost-vaccination Response*StimulatoryInhibitoryex vivo CD4/CD8IVS CD4/CD8Total Positive1NSCLC1.256010% / 40%100% / 20%100%2Bladder3.1516450% / 38%63% / 50%88%3Melanoma28.69199416% / 38%75% / TBDTBD4Bladder3.53181TBDTBDTBD5NSCLC3.5616955% / 45%TBDTBD*number of positive peptides/total peptides immunized Conclusions GEN-009 is a neoantigen vaccine that identifies tumor specific immune targets from the individual patient’s repertoire. Immunogenicity data show that ATLAS can, with very high frequency, identify relevant neoantigens and exclude suppressive peptides. Clinical vaccination with PD-1 blockade is in process. Clinical trial identification NCT03633110, issued 6-Aug-2018. Legal entity responsible for the study Genocea Biosciences. Funding Genocea Biosciences. Disclosure P. Twardowski: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Pfizer; Speaker Bure