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 the 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. Patients and Methods: This is a noncontrolled, 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 4 consecutive days and as an intralesional injection, 6 to 13 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 a confirmed partial response and one patient revealed an unconfirmed partial response 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 immunologic 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.

Upstream process optimization and micro- and macrocarrier screening for large-scale production of the oncolytic H-1 protoparvovirus

“…Patient treatment with the oncolytic parvovirus H-1PV has shown promising results in clinical trials against several types of cancers (Geletneky et al, 2017 ; Hajda et al, 2021 ). In preparation for market release, we sought to optimize the culture medium and production process at laboratory scale.…”

“…It demonstrated oncolytic and oncosuppressive properties during preclinical proof-of-concept studies in various cultured cell lines, and in animal (Rommelaere et al, 2010;Nuesch et al, 2012) and xenograft models against several human tumor species (Geletneky et al, 2010;Faisst et al, 1998;Angelova et al, 2009a,b;Dupressoir et al, 1989). H-1PV also showed safety and immunogenic activity in clinical phase I/ IIa studies (Geletneky et al, 2012, Geletneky et al, 2017 and phase II studies (Hajda et al, 2021). Considering a market release of H-1PV in the future, the production capacity must be increased and the process optimized.…”

Endoscopic ultrasound as a reliable tool for assessment of pancreatic adenocarcinoma treatment: Example of in situ gene therapy

“…Regardless of the good agreement between investigators in terms of tumor diameter, there was also perfect agreement with regard to the antitumor effect noted in the gene therapy trial by the principal investigator 6 . Although the effect was modest and is currently being assessed on a larger scale during the Phase 2 study (Thergap-2 trial), this method is indicative of an important area of investigation in line with the EUS-guided administration of local antitumor treatments such as gene therapy, radiofrequency, and chemotherapy 6 15 16 17 18 . A centralized system, therefore, can be established for future protocols, provided that a clearly defined, standardized EUS recording is obtained.…”

An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer

“…The inclusion criteria for this clinical trial was that all patients must have at least one hepatic metastatic lesion. The study was completed in 2018 (NCT02653313) and results are published ( 183 , 184 ) ( Table 2 ).…”