Shenzhen Hospital of University of Hong Kong Shenzhen, Guangzhou
Y. Zhang1, R. Li2, Y. F. Hu3, W. Dai4, J. Wang5, Z. Y. Xu6, X. Su7, J. Huang8,9, and F. M. Kong10,11; 1The University of Hong Kong-Shenzhen Hospital, Shenzhen, China, 2Geyuan Zhishan (Shanghai) Biotechnology Co., Ltd., Shanghai, Shanghai, China, 3BayVax Biotech Limited, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong, China, Hong Kong, Hong kong, China, 4Department of Clinical Oncology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, Hong Kong, Hong Kong, China, 5Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd., Shenzhen, China., Shenzhen, Guangdong, China, 6Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China, Shenzhen, Shenzhen, China, 7Department of Gastrointestinal Surgery, The Second Afliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China, Wenzhou, Zhejiang, China, 8Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese, Hong Kong, Hong Kong, China, 9School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Hong Kong, China, Hong Kong, Hong kong, China, 10The University of Hong Kong, Hong Kong, China, 11Department of Clinical Oncology, Hong Kong University Shenzhen Hospital, Shenzhen, China
Purpose/Objective(s): Neoantigen-based vaccine has shown amazing efficacy in some solid tumors such as melanoma, GBM, NSCLC and CRC. However, neoantigen vaccination has limited activity in stage IV patients, due to ineffective T-cell function and the large tumor burden. The hypothesis of our study is that in stage IV patients, neoantigen peptide vaccines combined with precision radiation therapy (CLERT), delivering optimized radiotherapy doses to tumor-critical regions in multifocal patients, can synergistically inhibit tumor growth. Our main research purpose was to evaluate and explore the anti -tumor activity of personalized tumor neoantigen peptide vaccine combined with radiotherapy in the treatment of patients with advanced malignant tumors. Materials/
Methods: Patients must meet all of the following inclusion criteria to be enrolled in this study: 1) Patients with advanced or recurrent tumors diagnosed by pathology and imaging, who have failed first-line treatments or have progressed; 2) Patients with expected survival =3 months and with ECOG (Eastern Cooperative Oncology Group) score was 0-2 points; 3) Patients had more than 1 predicted high-quality tumor neoantigen. This study is an open-label, multicenter phase II randomized study. Includes 2 cohorts: placebo + conventional treatment (including radiotherapy) group; Personalized tumor peptide vaccine + conventional treatment (including radiotherapy) group. Patients were stratified by first, second, and third-line treatment stages based on individual condition assessment, and then randomly entered two cohorts in a 1:1 ratio. In addition, after patients in cohort 1 have disease progression or ineffectiveness after the first-stage treatment, they can "cross-over" to cohort 2 for the second-stage personalized neoantigen peptide vaccine group + conventional treatment (including radiotherapy) through a one-way crossover experiment, and will evaluate response rates in both phases before and after crossover. Results: The clinical trial is initially designed to recruit 154 patients. It has obtained academic and ethical approval and obtained clinical trial registration number ChiCTR2300078055. Preliminary screening of 20 patients has been completed, and two people have been officially enrolled. It is currently recruiting. Conclusion: This clinical design of precision radiotherapy combined with tumor neoantigen vaccine will allow us to answer questions about vaccination efficacy and the impact of various radiation doses and expect to provide new opportunities for patients with advanced and refractory solid tumors.
