1631 - Randomized phase 2 clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients

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

UMIN000007905.

Editorial acknowledgement

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.