Abstract CT237: A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer
Authors: Liu Qin , Qian Hanqing , Shao Jie , Xu Qiuping , Sha Huizi , Yang Yang , Wang Weifeng , Yu Lixia , Liu Baorui , Wei Jia 
Published: September 2020

Abstract
Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer.
Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated.
Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. 10 of the 25 patients developed grade 1 local skin reactions with redness, swelling or subcutaneous indurations in the injection sites. Three patients were observed grade 2 local skin reactions in the injection sites. Four had grade 1 to 2 fever. No SAEs related to PVAC have been observed. Among median follow up time of 11.6 months (range: 7.5-24.0 months), only one patient had local recurrence at 10.5 months after surgery. The rest 24 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs.
Conclusions: PVAC is a multiple neoantigens/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient's capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319.
Citation Format: Qin Liu, Hanqing Qian, Jie Shao, Qiuping Xu, Huizi Sha, Yang Yang, Weifeng Wang, Lixia Yu, Baorui Liu, Jia Wei. A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT237.