Programmed cell death protein 1 (PD-1) inhibitors have modest efficacy as a monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 inhibitors through the induction of tumor-specific immunity. This phase 1/2 study evaluated a DNA plasmid PTCV (GNOS-PV02) encoding up to 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab in patients with advanced HCC. Safety, immunogenicity, efficacy, and feasibility were assessed. The treatment was well-tolerated, with the most common adverse events being injection-site reactions. The objective response rate was 30.6%, with 8.3% achieving complete response. Responses correlated with the number of neoantigens in the vaccine. Neoantigen-specific T cell responses were observed in most patients, with analysis revealing active, proliferative, and cytolytic vaccine-specific T cells. Results support the PTCV's mechanism of action and demonstrate clinical activity.

Mark Yarchoan, Edward J. Gane, Thomas U. Marron, Renzo Perales-Linares, Jian Yan, Neil Cooch, Daniel H. Shu, Elana J. Fertig, Luciane T. Kagohara, Gabor Bartha, Josette Northcott, John Lyle, Sarah Rochestie, Joann Peters, Jason T. Connor, Elizabeth M. Jaffee, Ildiko Csiki, David B. Weiner, Alfredo Perales-Puchalt, Niranjan Y. Sardesai