Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
BMJ Open. 2022 Jun 16;12(6):e060431. doi: 10.1136/bmjopen-2021-060431.
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.
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.
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.
NL9723.
晚期胰腺导管腺癌（PDAC）患者的预后较差，传统化疗治疗仅能有限地提高生存率。免疫疗法可能是我们目前治疗策略的补充。我们之前的研究表明，同种异体肿瘤裂解物树突状细胞（DC）疫苗与抗 CD40 激动性抗体联合使用可在 PDAC 小鼠模型中产生强大的抗肿瘤反应并带来生存获益。在鹿特丹 PancrEAtic Cancer Vaccination-2 试验中，我们旨在将我们的发现转化为患者。本研究旨在确定 DC/抗 CD40 激动性抗体联合治疗的安全性以及治疗引起的肿瘤特异性免疫反应。
这是一项开放标签、单中心（荷兰鹿特丹伊拉斯姆斯大学医学中心）、单臂、I 期剂量发现研究，纳入转移性胰腺腺癌成年患者，这些患者在接受 FOLFIRINOX 化疗后疾病进展。患者将接受加载同种异体肿瘤裂解物的单核细胞来源 DC 与 CD40 激动性抗体联合治疗。这种联合免疫治疗方案将每 2 周给药 3 次，在第 3 次注射后 3 个月和 6 个月进行加强治疗。将纳入至少 12 名和最多 18 名患者。主要终点是联合免疫治疗的安全性和耐受性。为了确定最大耐受剂量，将以固定剂量给予 DC，并根据传统的 3+3 剂量递增设计给予抗 CD40 激动剂。次要终点包括根据 RECIST（V.1.1）和 iRECIST 标准评估的放射学反应以及抗肿瘤特异性免疫反应的检测。
鹿特丹伊拉斯姆斯大学医学中心中央研究涉及人体伦理委员会（CCMO；NL76592.000.21）和医学伦理委员会（METC；MEC-2021-0566）批准了该试验的进行。所有参与者都需要书面知情同意。试验结果将提交给同行评议的科学期刊发表。
NL9723。
