PGV001, a Multi-Peptide Personalized Neoantigen Vaccine Platform: Phase I Study in Patients with Solid and Hematologic Malignancies in the Adjuvant Setting

Abstract Immunotherapies like immune checkpoint inhibitors (ICI) have changed the standard of care for patients with cancer, often leading to durable responses. However, many patients remain or become refractory to ICIs owing to factors such as a lack of primed neoantigen-reactive T cells. We developed a peptide-based vaccination platform that utilizes fully personalized genome vaccines (PGV) and targets neoantigens predicted by our OpenVax computational pipeline. In this study, we report results from the PGV001 study (NCT02721043) targeting up to 10 neoantigens, administered in the adjuvant setting to patients with both solid and hematologic malignancies who have high risk of recurrence. Our data indicate that PGV001 is feasible and safe, with 13 of 14 enrolled patients receiving the vaccine and 11 completing the treatment. 100% of vaccinated patients developed targeted T-cell and B-cell responses, highlighting the capacity of OpenVax to predict immunogenic neoantigens and the potential of PGV001 for safely inducing targeted immunity. Significance: The PGV001 platform is feasible, safe, and immunogenic. The OpenVax pipeline predicted immunogenic neoantigens in tumors with wide-ranging mutational burdens. Data from this study prompted three additional PGV001 trials, one in newly diagnosed glioblastoma, one in urothelial cancer in combination with an ICI, and another in prostate cancer.