Randomized phase II clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients

Abstract Background Since PD-1/PD-L1 blockade has displayed clinical efficacy in esophageal cancer patients, an immunological therapeutic approach such as a cancer vaccine will be realistic in clinics. NY-ESO-1, one of cancer-testis antigens, is expressed in approximately 30% esophageal squamous cell carcinoma (ESCC). Cholesteryl pullulan (CHP) is an antigen delivery system to antigen-presenting cells including macrophages. The complex of CHP and NY-ESO-1 protein (CHP-NY-ESO-1) is a vaccine that activates CD4+ and CD8+ T cells. We aimed to evaluate clinical efficacy of the CHP-NY-ESO-1 for esophageal cancer patients after radical surgery in a randomized phase II trial. Methods 54 NY-ESO-1-expressing ESCC patients who underwent radical surgery following neoadjuvant chemotherapy of cisplatin/5-FU were randomized to two arms, CHP-NY-ESO-1 vaccine and observation as a control arm. The vaccine was composed of 200 mg full-length NY-ESO-1 protein, which was subcutaneously given 15 doses with 2 or 4-week interval for 12 months. Primary endpoints were disease-free survival (DFS) and safety. Secondary endpoints were immune-responses and overall survival (OS). 49 patients were evaluated for DFS and OS. Results DFS in 2 years are 56.0% and 58.3% in the vaccine arm and in the control. OS in 2 years are 76.0% and 79.2%, respectively. No differences were seen between the vaccine and the control group. Subgroup analysis demonstrated that T-bet+ CD8+ T cell infiltration was significantly correlated to DFS and that PD-L1-expression in tumors showed unfavorable tendency for the vaccine group. Exploratory analysis of intra-cohort correlations among the vaccinated patients revealed that 5% or more expression of NY-ESO-1 and high polymeric immunoglobulin receptor (PIGR)-gene expression in tumors were favorable factors. Conclusions The clinical trial revealed that CHP-NY-ESO-1 vaccine alone did not display clinical efficacy compared to the control. It suggested that CHP-NY-ESO-1 vaccine would be indicated to > 5% NY-ESO-1 and/or high PIGR gene-expressing esophageal tumors that are infiltrated with activated T cells. Clinical trial identification UMI07905. Legal entity responsible for the study The authors. Funding Japan Agency for Medical Research and Development. Disclosure All authors have declared no conflicts of interest.