TY  - JOUR
AU  - Hajda, Jacek
AU  - Leuchs, Barbara
AU  - Angelova, Assia L
AU  - Frehtman, Veronika
AU  - Rommelaere, Jean
AU  - Mertens, Mieke
AU  - Pilz, Maximilian
AU  - Kieser, Meinhard
AU  - Krebs, Ottheinz
AU  - Huber, Bernard
AU  - Engeland, Christine
AU  - Mavratzas, Athanasios
AU  - Hohmann, Nicolas
AU  - Schreiber, Jutta
AU  - Jäger, Dirk
AU  - Halama, Niels
AU  - Sedlaczek, Oliver
AU  - Gaida, Matthias M
AU  - Daniel, Volker
AU  - Springfeld, Christoph
AU  - Ungerechts, Guy
TI  - Phase 2 trial of oncolytic H-1 parvovirus therapy shows safety and immune cell activity in patients with metastatic pancreatic ductal adenocarcinoma.
JO  - Clinical cancer research
VL  - 27
IS  - 20
SN  - 1557-3265
CY  - Philadelphia, Pa. [u.a.]
PB  - AACR
M1  - DKFZ-2021-01915
SP  - 5546-5556
PY  - 2021
N1  - 2021 Oct 15;27(20):5546-5556 / #LA:F230#
AB  - 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.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.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.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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34426438
DO  - DOI:10.1158/1078-0432.CCR-21-1020
UR  - https://inrepo02.dkfz.de/record/170408
ER  -