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)
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 a...
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BMJ Publishing Group
2022-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/6/e060431.full |
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| author | Joachim G J V Aerts Sjoerd H van der Burg Martijn P Lolkema Sai Ping Lau Freek R van ’t Land Marjolein Y V Homs Casper H J van Eijck |
| author_facet | Joachim G J V Aerts Sjoerd H van der Burg Martijn P Lolkema Sai Ping Lau Freek R van ’t Land Marjolein Y V Homs Casper H J van Eijck |
| author_sort | Joachim G J V Aerts |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-40029583d6574b97bc53298a9b94c429 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-40029583d6574b97bc53298a9b94c4292025-01-24T16:30:14ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-060431Safety 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)Joachim G J V Aerts0Sjoerd H van der Burg1Martijn P Lolkema2Sai Ping Lau3Freek R van ’t Land4Marjolein Y V Homs5Casper H J van Eijck61 Pulmonary Medicine, Erasmus Medical Center, Rotterdam, The NetherlandsOncode Institute, Utrecht, The NetherlandsDepartment of Medical Oncology, Erasmus MC, Rotterdam, The NetherlandsDepartment of Surgery, Erasmus MC, Rotterdam, The NetherlandsDepartment of Surgery, Erasmus MC, Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC, Rotterdam, The NetherlandsDepartment of Surgery, Erasmus Medical Center, Rotterdam, The NetherlandsIntroduction 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.https://bmjopen.bmj.com/content/12/6/e060431.full |
| spellingShingle | Joachim G J V Aerts Sjoerd H van der Burg Martijn P Lolkema Sai Ping Lau Freek R van ’t Land Marjolein Y V Homs Casper H J van Eijck 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) BMJ Open |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/12/6/e060431.full |
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