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Phase I/II trial of
intravenous OV001 oncolytic virus in resistant glioblastoma multiforme (GBM)
A. I. Freeman, J. M. Gomori, E. Linetsky, Z. Zakay-Rones, A. Panet, E.
Libson, C. S. Irving, E. Galun, T. Siegal
Hadassah University Hospital, Jerusalem, Israel; Hebrew
University, Jerusalem, Israel; OVCure (Israel) Ltd, Jerusalem, Israel; Savad
Institute of Gene Therapy Hadassah Hospital, Jerusalem, Israel; Gaffin Center
for Neuro-Oncology Hadassah Hospital, Jerusalem, Israel
Background.
OV001 (NDV HUJ) is an oncolytic, non-engineered, lentogenic
strain of Newcastle Disease Virus (NDV).
Following preclinical repetitive dosing toxicity studies,
a Phase I/II trial was initiated in GBM determining safety and imaging
response.
Methods.
Patients (11-58yrs, KPS 50-90%) with primary glioblastoma were
enrolled 17-49 wks following diagnosis and failure of previous therapy.
The first part of the study used an intra-patient dose
escalation method with one cycle dosage steps of 0.1, 0.5, 1, 5 and 10 BIU units
of OV001 (1 BIU = 1x109 EID50, 50% egg infectious
dose).
One cycle consisted of 15 min IV infusions on each of 5
consecutive days over a period of 7 d (<1BIU) or 14 d (>=1BIU).
Patient reaching 10 BIU received 3 additional cycles of 50
BIU.
Patients enrolled in the second part received three cycles
of 10 BIU.
Patients without progressive disease were maintained with
2 doses of 10 BIU IV weekly.
Results.
In Phase I, 4/6 patients completed all 3 cycles of 50 BIU of
OV001; in the Phase II part, as of Dec 01, 2003, 3/4 patients in Phase II part
completed all 3 cycles of 10 BIU.
Grade I/II constitutional fever was seen in 5 patients and
was the only adverse event related to OV001 administration.
MTD was not reached.
Patients that did not complete dosing were withdrawn due
to disease progression.
All tested patients developed anti-NDV hemagglutinin
antibodies after 7-14 days.
NDV was recovered from one tumor biopsy.
One patient has a continuing near complete response 30
weeks after start of dosing.
A second patient maintained stable disease between 16-26
weeks.
Conclusions.
Intravenous OV001 is well tolerated and most excitingly a
near complete response provides proof of concept of its therapeutic potential.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-00457,00.asp
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