A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer

Raghav Sundar; Sun Young Rha; Hiroki Yamaue; Masahiro Katsuda; Koji Kono; Hyo Song Kim; Chan Kim; Kousaku Mimura; Ley-Fang Kua; Wei Peng Yong

doi:10.1186/s12885-018-4234-8

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A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer

Authors: Raghav Sundar ; Sun Young Rha ; Hiroki Yamaue ; Masahiro Katsuda ; Koji Kono ; Hyo Song Kim ; Chan Kim ; Kousaku Mimura ; Ley-Fang Kua ; Wei Peng Yong

Citation: BMC CANCER, Vol.18(1) : 332, 2018-03

Journal Title: BMC CANCER

Issue Date: 2018-03

MeSH: Adult ; Aged ; Biomarkers ; Cancer Vaccines / adverse effects ; Cancer Vaccines / immunology* ; Cancer Vaccines / therapeutic use* ; Combined Modality Therapy ; Cytotoxicity, Immunologic ; Female ; HLA-A24 Antigen / genetics ; HLA-A24 Antigen / immunology ; Haplotypes ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Stomach Neoplasms / immunology* ; Stomach Neoplasms / mortality ; Stomach Neoplasms / pathology ; Stomach Neoplasms / therapy* ; T-Lymphocytes, Cytotoxic / immunology ; T-Lymphocytes, Cytotoxic / metabolism ; Vaccines, Subunit / immunology ; Vaccines, Subunit / therapeutic use

Keywords: Cancer vaccine ; Gastric cancer ; OTSGC-A24 ; Phase I

Abstract: Background: We conducted a phase I/Ib, open-label, single-arm trial to assess the safety, tolerability and optimal scheduling regimen of OTSGC-A24 cancer vaccine in patients with advanced gastric cancer.

Methods: Patients with advanced gastric cancer with HLA-A*24:02 haplotype were included in this study. OTSGC-A24 was administered at 1 mg in 3-weekly (3w), 2-weekly (2w), and weekly (1w) cohorts to evaluate the safety, immunological response and schedule. Based on the highest specific cytotoxic T lymphocyte (CTL) induction rate at 4 weeks, using the ELISPOT test, cohorts were expanded to define the optimal dosing schedule for OTSGC-A24.

Results: In this study, 24 advanced gastric cancer patients with HLA-A*24:02 haplotype were enrolled and treated in 3 cohorts (3w cohort: 3; 2w cohort: 11 and 1w cohort: 10 patients). The most common adverse events were decreased appetite (29%), diarrhea (21%), myalgia (25%). The most common treatment-related adverse event was injection site erythema (25%). No dose-limiting toxicities were observed in any cohort and OTSGC-A24 was well tolerated. Positive CTL responses after vaccination were observed in 15 patients (75%) at 4 weeks: 3w cohort (33%), 2w cohort (88%), 1w cohort (78%). At 12 weeks, 18 patients had responded (90%); 3w cohort (100%), 2w cohort (100%), 1w cohort (78%). The best radiological was stable disease (40%). Median progression free survival was 1.7 months (95% CI: 1.4 to 3.5) and median overall survival was 5.7 months (95% CI 3.8 to 8.6).

Conclusions: OTSGC-A24 combined peptide cancer vaccine was well tolerated. Significant responses in CTL were observed and the recommended phase 2 dose is 1 mg OTSGC-A24 sub-cutaneous, every 2 weeks. Although no radiological response was observed, a respectable overall survival was achieved, consistent with other immunotherapy agents being investigated in gastric cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT01227772 , Date registered: 21 Oct 2010.