Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma

Two peptide cocktail vaccines using glypican-3, WD-repeat-containing protein up-regulated in hepatocellular carcinoma (HCC) and nei endonuclease VIII-like three epitopes were evaluated in advanced HCC in two Phase I studies. Study 1 evaluated dose-limiting toxicities (DLTs) of peptides 1–3 (HLA-A24-restricted) and study 2 evaluated DLTs of peptides 1–6 (HLA-A24 or A02-restricted). Overall, 18 and 14 patients were enrolled in studies 1 and 2, respectively. No DLTs were observed up to 7.1 mg of the vaccine cocktail. No complete response/partial response was observed. Stable disease was reported in nine and five patients with a disease control rate of 52.9% and 35.7% in studies 1 and 2, respectively. Both vaccines showed good tolerability and potential usefulness against HCC. Clinical trial registration: ; Two peptide cocktail vaccines (ONO-7268MX1 [HLA-A24-restricted] and ONO-7268MX2 [HLA-A24 or A02-restricted]) were derived from parts of the hepatocellular carcinoma cells to trigger the body’s immune reaction against the cancer cells. Study 1 evaluated increasing doses that would cause toxicity of peptides 1–3 and study 2 evaluated the dose of peptides 1–6. Although, no complete response or partial response was observed, stable disease was reported in nine/18 and five/14 patients with a disease control rate of 52.9% and 35.7% in studies 1 and 2, respectively. Both vaccines showed good tolerability and potential usefulness against hepatocellular carcinoma.