肿瘤细胞治疗研究
英文原题：Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial).
Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial).
该联合免疫治疗方案将每2周给药一次，共3次，并在第3次注射后3个月和6个月给予加强治疗。
引言：晚期胰腺导管腺癌（PDAC）患者预后极差，传统化疗改善生存的效果有限。免疫治疗可能补充现有治疗策略。研究者此前在小鼠PDAC模型中显示，异基因肿瘤裂解物DC疫苗联合抗CD40激动型抗体可产生强效抗肿瘤应答并带来生存获益。Rotterdam PancrEAtic Cancer Vaccination-2（REACtiVe-2）试验旨在将该发现转化至患者。本研究将确定DC/抗CD40激动型抗体联合治疗的安全性，以及治疗诱导的肿瘤特异性免疫应答。方法与分析：这是一项开放标签、单中心（荷兰鹿特丹伊拉斯谟大学医学中心）、单臂、I期剂量探索研究。FOLFIRINOX化疗后疾病进展的转移性胰腺癌成人患者，将接受负载异基因肿瘤裂解物的单核细胞来源DC，并联合CD40激动型抗体。联合免疫治疗每2周给药一次，共3次；第3次注射后3个月和6个月进行加强治疗。计划纳入至少12例、最多18例患者。主要终点为联合免疫治疗的安全性和耐受性。为确定最大耐受剂量，DC剂量固定，抗CD40激动剂按传统3+3剂量递增设计给药。次要终点包括依据RECIST 1.1和iRECIST标准评估影像学应答，以及检测抗肿瘤特异性免疫应答。伦理与结果发布：中央人体研究委员会（CCMO；NL76592.000.21）及伊拉斯谟大学医学中心医学伦理委员会（METC；MEC-2021-0566）批准开展试验。所有参与者均须提供书面知情同意。研究结果将提交至同行评审科学期刊发表。试验注册号：NL9723。
INTRODUCTION: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) is dismal and conventional chemotherapy treatment delivers limited survival improvement. Immunotherapy may complement our current treatment strategies. We previously demonstrated that the combination of an allogeneic tumour-lysate dendritic cell (DC) vaccine with an anti-CD40 agonistic antibody resulted in robust antitumour responses with survival benefit in a murine PDAC model. In the Rotterdam PancrEAtic Cancer Vaccination-2 trial, we aim to translate our findings into patients. This study will determine the safety of DC/anti-CD40 agonistic antibody combination treatment, and treatment-induced tumour-specific immunological responses. METHODS AND ANALYSIS: In this open-label, single-centre (Erasmus Univsersity Medical Center, Rotterdam, Netherlands), single-arm, phase I dose finding study, adult patients with metastatic pancreatic cancer with progressive disease after FOLFIRINOX chemotherapy will receive monocyte-derived DCs loaded with an allogeneic tumour lysate in conjunction with a CD40 agonistic antibody. This combination-immunotherapy regimen will be administered three times every 2 weeks, and booster treatments will be given after 3 and 6 months following the third injection. A minimum of 12 and a maximum of 18 patients will be included. The primary endpoint is safety and tolerability of the combination immunotherapy. To determine the maximum tolerated dose, DCs will be given at a fixed dosage and anti-CD40 agonist in a traditional 3+3 dose-escalation design. Secondary endpoints include radiographic response according to the RECIST (V.1.1) and iRECIST criteria, and the detection of antitumour specific immune responses. ETHICS AND DISSEMINATION: The Central Committee on Research Involving Human Subjects (CCMO; NL76592.000.21) and the Medical Ethics Committee (METC; MEC-2021-0566) of the Erasmus M.C. University Medical Center Rotterdam approved the conduct of the trial. Written informed consent will be required for all participants. The results of the trial will be submitted for publication in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NL9723.
MEMBER ACCOUNT
登录成功会直接打开下一页。
