Phase I Trial Of Cancer Vaccine With Multiple Peptides Derived From Novel Onco-Antigen And Anti-Angiogenic Antigens For Patients With Advanced Non-Small Cell Lung Cancer (Nsclc).

e13015 Background: Two phase I clinical trials were conducted on patients with advanced or recurrent NSCLC to evaluate the safety, immunogenicity and clinical response of a multiple peptide vaccine that incorporates four epitope peptides. This vaccine is comprised of novel HLA-A24-restricted oncoantigens, including two of the following three peptides; up-regulated lung cancer 10 (URLC10), TTK protein kinase (TTK) and cell division associated 1 (CDCA1), in addition to peptides derived from vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). Methods: Peptides derived from URLC10, TTK, VEGFR1 and VEGFR2 were tested in Trial 1, while peptides derived from URLC10, CDCA1, VEGFR1 and VEGFR2 were tested in Trial 2. Fifteen HLA-24-positive patients with NSCLC who had not responded to standard therapy were enrolled in this classic 3 patient per dose per cohort phase I trial, designed with varying dosages (Trial 1; 0.5mg, 1mg and 3mg, Trial 2; 1mg, 3mg). Vaccines were administered weekly by subcutaneous injection into patients’ axillary region with Montanide ISA-51 incomplete Freund’s adjuvant until progressive disease occurred and/or patients refused further treatment. Immunological responses were evaluated by INF-gamma ELiSPOT assays. Results: Vaccinations were well-tolerated withno severe treatment-associated adverse events. Specific T cell responses were induced in all patients against at least one epitope peptide. However, weak immunological responses were found in the 0.5mg group compared with the 1mg and 3mg groups in Trial 1, therefore the 0.5mg group was excluded in Trial 2. In terms of clinical responses, no complete and partial responses were found, however 9 of 15 patients (60 %) were categorized with stable disease. The median overall survival time was 13.2 months, while 1- and 2-year survival rates were 52.5% and 32.8% respectively. Conclusions: Multiple peptide vaccination therapy using four novel peptides was safe, and could possibly be effective in extending the patients’ survival. These encouraging immunological and clinical responses could provide a case for further stages of clinical trials.