Multicenter phase 1-2 trial of the combination of personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma

PD-1 inhibitors have modest efficacy as a monotherapy for hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 inhibitors through the induction of tumor-specific immunity. The multicenter phase 1-2 GT-30 trial evaluated a DNA plasmid PCTV encoding up to 40 neoantigens (identified through sequencing tumor DNA and RNA of the individual patients) intradermally coadministered with plasmid-encoded interleukin 12 plus pembrolizumab in advanced HCC patients previously treated with a multityrosine kinase inhibitor. The most common treatment-related adverse events were injection-site reactions, observed in 41,6% of the patients. There were no dose-limiting toxicities of grade ≥ 3 TRAEs. Objective response was seen in 30.6% and complete response in 8.3%. Median time to response was 9.3 weeks (range 8-46), median progression-free survival was 4.2 months, and median overall survival was 19.9 months. Clinical responses were associated with the number of neoantigens encoded in the vaccine. The authors conclude that a PTCV plus pembrolizumab had clinical activity in advanced HCC.