Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer

BACKGROUND: We previously developed an immunotherapy treatment utilizing a cancer vaccine reagent KIF20A-66 in order to treat pancreatic cancer. KIF20A-66 is HLA-A24-restricted epitope peptide derived from KIF20A, a member of kinesin super family protein 20A that is significantly transactivated in pancreatic cancer. In this report, we further demonstrated non-randomized, open-label, single centered phase I/II clinical trial of immunotherapy using the KIF20A-66 peptide for the patients with advanced pancreatic cancer. METHODS: Vaccination was performed to the patients with metastatic pancreatic cancer, in whom gemcitabine-based therapy had failed. In phase I study, KIF20A-66 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 1.0 and 3.0 mg/body, 6 patients/1 cohort). After safety was assessed, phase II study was conducted using 3.0 mg of KIF20A-66 peptide. RESULTS: KIF20A-66 peptide vaccination was well tolerated in the doses we examined and tumor responses after 1 month of the treatment were evaluated. Among 29 patients who completed one course of the treatment at least, stable disease (SD) was found in 21 cases, while progressive disease (PD) was found in 8 cases, indicating that the disease control rate was 72%. Objective tumor shrinkage was observed in 8 cases, including 1 case of complete response (CR). The median survival time (MST) and progression free survival time (PFS) were 142 days and 56 days, respectively. These results clearly demonstrate that overall survival of the patients was significantly prolonged, compared to the historical controls of 9 cases with unmatched HLA in the same hospital (MST: 83 days), as well as 81 cases in our and other hospitals (MST: 63 days). CONCLUSION: The patients vaccinated with KIF20A-66 peptide had better prognosis than the control group with best supportive care (BSC). Thus, we concluded that KIF20A-66 vaccination is significantly effective as an immunotherapy against advanced pancreatic cancer. KIF20A-66 peptide was well tolerable in the dose of either 1.0 mg or 3.0 mg/body, and effectively induced peptide-specific response of cytotoxic T lymphocyte (CTL). Further clinical study using this peptide is a promising approach for advanced pancreatic cancer to achieve high potential benefit for better prognosis. CLINICAL TRIAL REGISTRATION: UMIN-CTR, number UMIN000004919