TY - JOUR
T1 - Irreversible electroporation and nivolumab combined with intratumoral administration of a toll‐like receptor ligand, as a means of in vivo vaccination for metastatic pancreatic ductal adenocarcinoma (Panfire‐iii). a phase‐i study protocol
AU - Geboers, Bart
AU - Timmer, Florentine E. F.
AU - Ruarus, Alette H.
AU - Pouw, Johanna E. E.
AU - Schouten, Evelien A. C.
AU - Bakker, Joyce
AU - Puijk, Robbert S.
AU - Nieuwenhuizen, Sanne
AU - Dijkstra, Madelon
AU - van den Tol, M. Petrousjka
AU - de Vries, Jan J. J.
AU - Oprea‐lager, Daniela E.
AU - Menke‐van der Houven van Oordt, C. Willemien
AU - on behalf of the Dutch Pancreatic Cancer Group
AU - van der Vliet, Hans J.
AU - Wilmink, Johanna W.
AU - Scheffer, Hester J.
AU - de Gruijl, Tanja D.
AU - Meijerink, Martijn R.
N1 - Funding Information: Acknowledgments: Figure 1 was created by Dana Hamers Scientific Arts and illustration was funded by AngioDynamics. Figure 4 was created with BioRender.com (accessed on 28 June 2021). Guus A.M.S. van Dongen (department of Radiology and Nuclear medicine, Amsterdam University Medical Centers, Cancer Center Amsterdam, the Netherlands) significantly contributed to the acquisition of funding and PET tracer side‐study design. Funding Information: Funding: This research is funded by Cancer Center Amsterdam grant number CCA2018‐5‐44 and Adessium Foundation grant number CCA2019‐5‐56. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Irreversible electroporation (IRE) is a novel image‐guided tumor ablation technique with the ability to generate a window for the establishment of systemic antitumor immunity. IRE transiently alters the tumor’s immunosuppressive microenvironment while simultaneously generating antigen release, thereby instigating an adaptive immune response. Combining IRE with immunotherapeutic drugs, i.e., electroimmunotherapy, has synergistic potential and might induce a durable antitumor response. The primary objective of this study is to assess the safety of the combination of IRE with IMO‐2125 (a toll‐like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this randomized controlled phase I clinical trial, 18 patients with mPDAC pretreated with chemotherapy will be enrolled in one of three study arms: A (control): nivolumab monotherapy; B: percutaneous IRE of the primary tumor followed by nivolumab; or C: intratumoral injection of IMO‐2125 followed by percutaneous IRE of the primary tumor and nivolumab. Assessments include contrast enhanced computed tomography (ceCT),18F‐FDG and18F‐BMS‐986192 (PD‐L1) positron emission tomography (PET)‐CT, biopsies of the primary tumor and metastases, peripheral blood samples, and quality of life and pain questionnaires. There is no curative treatment option for patients with mPDAC, and palliative chemotherapy regimens only moderately improve survival. Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti‐tumor response, it may ultimately improve PDAC’s dismal prognosis.
AB - Irreversible electroporation (IRE) is a novel image‐guided tumor ablation technique with the ability to generate a window for the establishment of systemic antitumor immunity. IRE transiently alters the tumor’s immunosuppressive microenvironment while simultaneously generating antigen release, thereby instigating an adaptive immune response. Combining IRE with immunotherapeutic drugs, i.e., electroimmunotherapy, has synergistic potential and might induce a durable antitumor response. The primary objective of this study is to assess the safety of the combination of IRE with IMO‐2125 (a toll‐like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this randomized controlled phase I clinical trial, 18 patients with mPDAC pretreated with chemotherapy will be enrolled in one of three study arms: A (control): nivolumab monotherapy; B: percutaneous IRE of the primary tumor followed by nivolumab; or C: intratumoral injection of IMO‐2125 followed by percutaneous IRE of the primary tumor and nivolumab. Assessments include contrast enhanced computed tomography (ceCT),18F‐FDG and18F‐BMS‐986192 (PD‐L1) positron emission tomography (PET)‐CT, biopsies of the primary tumor and metastases, peripheral blood samples, and quality of life and pain questionnaires. There is no curative treatment option for patients with mPDAC, and palliative chemotherapy regimens only moderately improve survival. Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti‐tumor response, it may ultimately improve PDAC’s dismal prognosis.
KW - Ablation
KW - Checkpoint inhibition
KW - CpG‐ODN
KW - IMO‐2125
KW - Immunotherapy
KW - Irreversible electroporation (IRE), nivolumab
KW - Metastatic pancreatic cancer
KW - PDAC
KW - PET‐C
KW - Toll‐like receptor ligand
UR - http://www.scopus.com/inward/record.url?scp=85111446648&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers13153902
DO - https://doi.org/10.3390/cancers13153902
M3 - Article
C2 - 34359801
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 15
M1 - 3902
ER -