Abstract 1631
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.
Resources from the same session
4543 - Long-term real-world (RW) outcomes in patients with advanced melanoma (MEL) treated with ipilimumab (IPI) and non-IPI therapies: IMAGE study
Presenter: Stéphane Dalle
Session: Poster Display session 3
Resources:
Abstract
4523 - Prognostic Factors for efficacy of Ipilimumab used after AntiPD1 and/or BRAF+MEK inhibitors in Melanoma Patients: an Italian Melanoma Intergroup study
Presenter: Riccardo Marconcini
Session: Poster Display session 3
Resources:
Abstract
3632 - Rechallenge with combination ipilimumab and anti-PD-1 (IPI+PD1) in metastatic melanoma after acquired resistance to IPI+PD1 immunotherapy
Presenter: Adriana Hepner
Session: Poster Display session 3
Resources:
Abstract
3732 - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy.
Presenter: Kazi Nahar
Session: Poster Display session 3
Resources:
Abstract
5005 - Real-world outcomes of ipilimumab plus nivolumab for advanced melanoma in the Netherlands
Presenter: Michiel van Zeijl
Session: Poster Display session 3
Resources:
Abstract
5524 - Utilization of Real-World Data to Assess the Effectiveness of Immune Checkpoint Inhibitors (ICIs) in Elderly Patients with Metastatic Melanoma
Presenter: D Scott Ernst
Session: Poster Display session 3
Resources:
Abstract
5884 - Tumor mutational burden and response to PD-1 inhibitors: an analysis of 89 cases of metastatic melanoma.
Presenter: Léa Dousset
Session: Poster Display session 3
Resources:
Abstract
3120 - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma.
Presenter: Elisa Rozeman
Session: Poster Display session 3
Resources:
Abstract
2157 - Immune status defined by molecular information layers predicts response to pembrolizumab treatment in advanced melanoma
Presenter: Guillermo Prado-Vázquez
Session: Poster Display session 3
Resources:
Abstract
2553 - Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy
Presenter: Shahneen Sandhu
Session: Poster Display session 3
Resources:
Abstract