Phase 1 study of OCV-C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

Hiroya Taniguchi, Satoru Iwasa, Kentaro Yamazaki, Takayuki Yoshino, Chika Kiryu, Yoshiharu Naka, Ei Leen Liew, Yuh Sakata, Hiroya Taniguchi, Satoru Iwasa, Kentaro Yamazaki, Takayuki Yoshino, Chika Kiryu, Yoshiharu Naka, Ei Leen Liew, Yuh Sakata

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.

Trial registrations: JAPIC clinical trials registry (ID: JapicCTI-132075) and ClinicalTrials.Gov (ID: NCT01801930).

Keywords: Colorectal cancer; OCV-C02; RNF43; TOMM34; peptide vaccine.

© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Figures

Figure 1
Figure 1
Time to treatment failure. Median time (months) to treatment failure of 24 patients with advanced or relapsed colorectal cancer treated with OCV‐C02 at doses of 0.3, 1, 3, and 6 mg/body.
Figure 2
Figure 2
Overall survival. Median overall survival (months) of 24 patients with advanced or relapsed colorectal cancer treated with OCV‐C02 at doses of 0.3, 1, 3, and 6 mg/body. One patient each in cohort 2 (1 mg/body) and cohort 4 (6 mg/body) were treated as censored cases.

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