title: Phase 1 study of OCV-C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer.
abstract: OCV-C02 is a peptide vaccine consisting of two peptide epitopes derived from ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34 (TOMM34). This Phase 1 study assessed the safety, preliminary efficacy and immunological responses following OCV-C02 administration in patients with advanced or relapsed colorectal cancer who were intolerant or refractory to standard chemotherapy. Primary endpoint was any occurrence of dose-limiting toxicity (DLT) during cycle 1. Secondary endpoints were treatment-emergent adverse events, efficacy and immunological responses. Efficacy was evaluated based on overall response rate, disease control rate, time to treatment failure and overall survival. Immunological responses were evaluated by measuring CTL, delayed-type hypersensitivity (DTH) and regulatory T cells (Tregs). Twenty-four patients who were HLA-A*24:02-positive were enrolled and grouped into four cohorts of six patients each: cohorts 1, 2, 3, and 4 which received s.c. OCV-C02 (emulsifying agent: Montanide™ ISA 51 VG) 0.3, 1, 3, and 6 mg/body, respectively. After cycle 1, patients who were eligible and willing to continue vaccination proceeded to the extended treatment period. No DLT occurred in cycle 1 and no major safety problems were reported throughout the trial. One patient in cohort 2, three patients in cohort 3 and two patients in cohort 4 achieved stable disease. CTL and DTH responses following vaccination were also observed across the four cohorts. OCV-C02 at 0.3 to 6 mg/body was found to be safe and well tolerated.
  
  
  BACKGROUND
  JAPIC clinical trials registry (ID: JapicCTI-132075) and ClinicalTrials.Gov (ID: NCT01801930).
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Gastroenterology & Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Department of Clinical Management, Headquarters of Clinical Development, Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kiryu
authors.affiliation: Department of Clinical Development - Oncology, Headquarters of Clinical Development, Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Naka
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: Ei Leen
authors.identifier: http://orcid.org/0000-0002-8356-9790
authors.initials: EL
authors.lastname: Liew
authors.affiliation: Department of Medical Oncology, Misawa-City Hospital, Aomori, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D059871:HLA-A24 Antigen / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010455:Peptides
keywords: Colorectal cancer; OCV-C02; RNF43; TOMM34; peptide vaccine