Taniguchi Hiroya, Iwasa Satoru, Yamazaki Kentaro, Yoshino Takayuki, Kiryu Chika, Naka Yoshiharu, Liew Ei Leen, Sakata Yuh
Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
Cancer Sci. 2017 May;108(5):1013-1021. doi: 10.1111/cas.13227. Epub 2017 May 11.
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.
JAPIC clinical trials registry (ID: JapicCTI-132075) and ClinicalTrials.Gov (ID: NCT01801930).
OCV-C02是一种肽疫苗，由来自环指蛋白43（RNF43）和线粒体外膜转位酶34（TOMM34）的两个肽表位组成。这项1期研究评估了在对标准化疗不耐受或难治的晚期或复发性结直肠癌患者中给予OCV-C02后的安全性、初步疗效和免疫反应。主要终点是第1周期期间任何剂量限制性毒性（DLT）的发生。次要终点是治疗中出现的不良事件、疗效和免疫反应。疗效基于总缓解率、疾病控制率、治疗失败时间和总生存期进行评估。通过测量细胞毒性T淋巴细胞（CTL）、迟发型超敏反应（DTH）和调节性T细胞（Tregs）来评估免疫反应。招募了24名HLA-A*24:02阳性患者，并将其分为四个队列，每个队列6名患者：队列1、2、3和4，分别接受皮下注射OCV-C02（乳化剂：Montanide™ ISA 51 VG）0.3、1、3和6 mg/体。第1周期后，符合条件且愿意继续接种疫苗的患者进入延长治疗期。第1周期未发生DLT，整个试验期间未报告重大安全问题。队列2中的1名患者、队列3中的3名患者和队列4中的2名患者病情稳定。在四个队列中也观察到了接种疫苗后的CTL和DTH反应。发现0.3至6 mg/体的OCV-C02安全且耐受性良好。
日本药品和医疗器械综合机构（PMDA）临床试验注册库（ID：JapicCTI-132075）和美国国立医学图书馆（NLM）临床试验注册库（ID：NCT01801930）。
