1152P - Phase 1 study of HSP105-derived peptide vaccine for patients with advanced esophageal cancer/ colo- rectal cancer.

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Drug Development
Cancer in Adolescents
Oesophageal Cancer
Presenter Satoshi Wada
Citation Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376
Authors S. Wada1, T. Kojima2, T. Nakatsura3, H. Bando2, O. Motohashi4, M. Shimomura3, T. Yoshikawa3, K. Kohashi5, A. Hori6, H. Ono7, M. Fukutani7, M. Wakabayashi7, S. Nomura7, A. Sato7, T. Sasada1, A. Ohtsu2
  • 1Cancer Immunotherapy, Kanagawa Cancer Center, 2418515 - Yokohama/JP
  • 2Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba/JP
  • 3Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center , National Cancer Center, Chiba/JP
  • 4Gastroenterology, Kanagawa Cancer Center, 2418515 - Yokohama/JP
  • 5Anatomic Pathology, Kyushu University, Fukuoka/JP
  • 6Cancer Vaccine Center, Kanagawa Cancer Center, 2418515 - Yokohama/JP
  • 7Clinical Research Support Office, National Cancer Center Hospital East, Chiba/JP

Abstract

Background

The HSP105 protein has been identified in pancreatic cancer by the SEREX method, and this protein has also been reported to play a role in controlling apoptosis in cancer cells. HSP105 is highly expressed in various human cancers, including colorectal cancer, esophageal cancer, pharyngeal cancer, pancreatic cancer, breast cancer, and melanoma. We have therefore identified the respective HSP105-derived peptides that bind to HLA-A24 and HLA-A2(EP1536006, JP5112615, JP5291641, US9,404,925). We investigated the safety and efficacy of HSP105-derived peptide vaccine for patients ((pts)) with advanced esophageal cancer/colo-rectal cancer.

Methods

We conducted a multicenter phase 1 study of HSP105-derived peptide vaccine for pts with advanced esophageal cancer/colo- rectal cancer. The recommended dose is determined based on the incidence of dose-limiting toxicity (DLT) during phase 1a (P1a). Pts will then be added in phase 1b (P1b) to investigate the safety and efficacy of the vaccine. The vaccine was injected intradermally every 7 days. The primary objective of this study was to evaluate DLT (P1a), response rate (P1b). Progression-free survival, treatment failure rate, and toxicity were also evaluated as secondary objectives. As exploratory endpoint, immunological effect was investigated.

Results

A total 30 pts (HLA-24 group 15pts, HLA-02 group 15 pts) were enrolled and grouped into level 1 which received intradermally administration of peptide vaccine (emulsifying agent: Montanide ISA 51 VG) 3 mg/body. No DLT occurred and no major safety problems were reported throughout the trial. Although pts with objective clinical efficacy was not apparent, 7 pts showed stable disease 2 months after initiation of treatment. The HSP105-derived peptide vaccine induced HSP105-specific CTL response in 15 pts (50%) of 30 pts. Additionally, we established several HSP105 peptide-specific CTL clones from PBMCs and tumor of pts vaccinated with HSP105 peptide by single cell sorting using Dextramer or anti-CD107a antibody.

Conclusions

Although objective clinical efficacy was not apparent, HSP105-derived peptide vaccine appears safe and well tolerated with minimal local toxicity.

Clinical trial identification

Protocol number: UMIN000017809, Release date: Jun 22, 2015

Legal entity responsible for the study

National Cancer Center

Funding

1. Health and Labor Science Research Grants for Research for Promotion of Cancer Control Programmes from the Ministry of Health, Labor and Welfare (2014). 2. Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development, AMED (2015, 2016).

Disclosure

All authors have declared no conflicts of interest.