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

Bart Geboers; Florentine E F Timmer; Alette H Ruarus; Johanna E E Pouw; Evelien A C Schouten; Joyce Bakker; Robbert S Puijk; Sanne Nieuwenhuizen; Madelon Dijkstra; M Petrousjka van den Tol; Jan J J de Vries; Daniela E Oprea-Lager; C Willemien Menke-van der Houven van Oordt; Hans J van der Vliet; Johanna W Wilmink; Hester J Scheffer; Tanja D de Gruijl; Martijn R Meijerink; On Behalf Of The Dutch Pancreatic Cancer Group

doi:10.3390/cancers13153902

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

Cancers (Basel). 2021 Aug 2;13(15):3902. doi: 10.3390/cancers13153902.

Authors

Bart Geboers¹, Florentine E F Timmer¹, Alette H Ruarus¹, Johanna E E Pouw², Evelien A C Schouten¹, Joyce Bakker², Robbert S Puijk¹, Sanne Nieuwenhuizen¹, Madelon Dijkstra¹, M Petrousjka van den Tol³, Jan J J de Vries¹, Daniela E Oprea-Lager¹, C Willemien Menke-van der Houven van Oordt², Hans J van der Vliet^{2

4}, Johanna W Wilmink², Hester J Scheffer¹, Tanja D de Gruijl², Martijn R Meijerink¹, On Behalf Of The Dutch Pancreatic Cancer Group

Affiliations

¹ Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
² Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
³ Department of Surgery, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
⁴ Lava Therapeutics, Yalelaan 60, 3584 CM Utrecht, The Netherlands.

Abstract

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 and ¹⁸F-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.

Keywords: CpG-ODN; IMO-2125; PDAC; PET-C; ablation; checkpoint inhibition; immunotherapy; irreversible electroporation (IRE); metastatic pancreatic cancer; nivolumab; toll-like receptor ligand.

Abstract

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