Phase I Study Of The Safety And Immunogenicity Of Personalized Neoantigen Vaccines And Tumor Treating Fields In Patients With Newly Diagnosed Glioblastoma

Abstract BACKGROUND Glioblastoma (GBM) generates mutation-derived tumor antigens, which arise from somatic variants that result in mutated protein fragments displayed to immune cells. These mutated proteins can provide targets for anti-tumor personalized neoantigen vaccine (PNV) therapy. Combining PNV with Tumor Treating Fields (TTFields), a modality that increases survival of GBM patients, is a viable option. METHODS In this phase I study (NCT03223103), PNV and TTFields are combined with the standard treatment for newly diagnosed GBM. Neoantigens are identified using the OpenVax computational pipeline, which identifies somatic variants in a patient’s DNA and ranks resulting neoantigens by their tumor RNA abundance and predicted HLA-I binding affinity. Each patient is vaccinated with up to 10 mutated peptides, receiving 14 doses of PNV administered subcutaneously with poly-ICLC as the adjuvant. RESULTS We report our preliminary results in the 8 patients with median age 59 (range 32–84) that have been vaccinated. Neoantigens were identified in each tumor sample in sufficient quantities for vaccination, with each vaccine comprising a median of 8.5 peptides (range 6–10). Patients received a median of 13 vaccines (range 8–14). Immune monitoring for one of the patients showed neoantigen-specific CD4 and CD8 T cell responses. There was radiological tumor progression in two while receiving PNV and in another, prior to PNV. The most common adverse events of the PNV were injection site reaction and flu-like symptoms. Combination with TTFields did not increase toxicity. The Kaplan-Meier estimated 12-month progression-free survival is 62.5% (s.e.= 17.1%) and the estimated 12-month survival from date of surgery is 83.3% (s.e.= 16.7%). The median survival has not been reached. CONCLUSIONS Despite a typically low mutational burden of GBM, selection of a sufficient number of neoantigens was successful for each patient’s vaccine. Treatment with PNV and TTFields is safe. The data is encouraging and updated results will be presented.