Phase 2 trial of oncolytic H-1 parvovirus therapy shows safety and signs of immune system activation in patients with metastatic pancreatic ductal adenocarcinoma

Abstract

Purpose: To investigate safety, clinical efficacy, virus pharmacokinetics, shedding and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy. Experimental Design: This is a non-controlled, single arm, open label, dose-escalating, single center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on four consecutive days and as intralesional injection, six to thirteen days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28. Results: ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had confirmed partial response (PR) and one patient revealed unconfirmed PR according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose-dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T cell responses to viral proteins. An interesting immunological pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx. Conclusions: The trial met all primary objectives, revealed no environmental risks and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.