Abstract
BackgroundWe 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.MethodsPatients 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.ResultsIn 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).ConclusionsOTSGC-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 registrationClinicalTrials.gov Identifier: NCT01227772, Date registered: 21 Oct 2010.
Highlights
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
Four cancer specific antigens Forkhead box protein M1 (FOXM1), DEP domain-containing protein 1 (DEPDC1), Kinesin family member 20A (KIF20A), and Upregulated in lung cancer 10 (URLC10) were identified based on differential expression in Gastric cancer (GC) samples versus normal tissue based on cDNA arrays and immunohistochemical staining
It has been shown that the cytotoxic T lymphocyte (CTL) clones established from these CTLs recognize Human leukocyte antigen (HLA)-A24-positive cells that endogenously express FOXM1, DEPDC1, KIF20A, or URLC10, respectively in a dose dependent manner [10]. These results suggest that a cancer vaccine therapy with these peptides would induce specific CTLs and exhibit antitumor effect
Summary
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. The 5-year overall survival (OS) for patients with unresectable GC due to locally advanced disease or metastatic spread ranges from 5 to 15% [1, 2]. In this group of patients, palliative chemotherapy has been demonstrated to prolonged survival when compared with. Tumor cells frequently express tumor specific antigens. These antigens are potential targets for immunotherapy.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
