– The TARDOX Study, in Collaboration
with University of Oxford, Evaluates the Use of Focused Ultrasound
in Combination with ThermoDox® to Treat Primary and Metastatic
Liver Cancer –
Celsion Corporation (NASDAQ: CLSN), an oncology drug development
company, today announced that results from a Phase I trial of
ThermoDox® were published in the peer-reviewed journal, The Lancet
Oncology ¹. Conducted by a multi-disciplinary team of biomedical
engineers, oncologists, radiologists and anesthetists at the
University of Oxford, United Kingdom, the trial evaluated the
safety and efficacy of ThermoDox®, Celsion’s proprietary
heat-activated liposomal encapsulation of doxorubicin, along with
focused ultrasound for the treatment of liver cancer. Referred to
as the TARDOX Study, the trial demonstrated that the ThermoDox®
plus focused ultrasound technique increased doxorubicin delivery to
tumors between two- and ten-fold in the majority of patients in
this 10-patient trial.
“Reaching therapeutic levels of cancer drugs
within a tumor, while avoiding side effects for the rest of the
body is a challenge for all cancer drugs, including small
molecules, antibodies and viruses,” said Professor Constantin
Coussios, Director of the Oxford Centre for Drug Delivery Devices
(OxCD3) and of the Institute of Biomedical Engineering at the
University of Oxford. “Our study is the first to trial this new
technique in humans and finds that it is possible to safely trigger
and target the delivery of chemotherapy deep within the body from
outside the body using focused ultrasound. Once inside the tumor,
the drug is released from the carrier, supplying a higher dose of
chemotherapy directly to the tumor, which may help to treat tumors
more effectively for the same or a lower systemic dose of the
drug.”
“The findings published in The Lancet Oncology
prove that ThermoDox® combined with targeted thermal therapy can
increase the concentration of doxorubicin up to 10 times in actual
tumors in liver cancer patients,” said Nicholas Borys, M.D.,
Celsion's senior vice president and chief medical officer. “The
most dramatic finding was that a single dose of thermally activated
ThermoDox® produced a clinical response in some of the tumors
treated.”
A lysolipid thermally sensitive liposome
encapsulating the chemotherapy agent, doxorubicin, ThermoDox® is
designed to release targeted levels of doxorubicin into and around
liver tumors with heat activation. In this Phase I study, and
consistent with the ThermoDox® heat-activated design, the amount of
drug passively reaching the tumor was low and estimated to be below
therapeutic levels before ultrasound exposure. Following focused
ultrasound application with ThermoDox®, chemotherapy concentrations
within the liver tumor were between two and ten times higher in
seven out of 10 patients, with an average increase of 3.7 times
across all patients.
“Only low levels of chemotherapy entered the
tumor passively. The combined thermal and mechanical effects of
ultrasound not only significantly enhanced the amount of
doxorubicin that entered the tumor, but also greatly improved its
distribution, enabling increased intercalation of the drug with the
DNA of cancer cells,” explained Dr. Paul Lyon, clinical research
fellow at the Nuffield Department of Surgical Sciences at the
University of Oxford and lead author of the study.
The Phase I trial evaluated patients with
inoperable primary or secondary liver tumors and who had previously
received chemotherapy. The procedure was carried out under general
anaesthesia, and patients received a single intravenous dose of 50
mg/m2 of ThermoDox®. The target tumor was selectively heated to
over 39.5o C using an approved ultrasound-guided focused ultrasound
device at the Churchill Hospital in Oxford. In six patients, the
temperature at the target tumor was monitored using a temporarily
implanted probe, while in the remaining four patients, ultrasonic
heating was carried out non-invasively. Side effects were monitored
for 30 days after the procedure, and apart from the existing side
effects caused by general anesthetic and chemotherapy, no
additional side effects were observed. Five patients experienced
grade 4 neutropenia, but their symptoms were resolved without
treatment, and one patient experienced mild confusion after the
procedure, which was resolved.
“This study adds to the ever growing body of
evidence supporting thermally activated ThermoDox® has the
potential to deliver potent and concentrated levels of doxorubicin
to liver tumors – an effect that we believe may result in enhanced
tumor killing,” said Michael H. Tardugno, Celsion's chairman,
president and chief executive officer. “The efficacy of ThermoDox®
continues to be evaluated, and the OPTIMA Study, a 550-patient,
multinational, double-blind, placebo-controlled, pivotal Phase III
clinical study of ThermoDox® in combination with radiofrequency
ablation (RFA), is well underway. The OPTIMA Study will evaluate
overall survival in patients with primary liver cancer. We expect
to complete enrollment in this pivotal study in the third quarter
of 2018 and look forward to the first prespecified interim efficacy
analysis in the first half of 2019.”
The TARDOX Study, supported by the National
Institute for Health Research (NIHR) Oxford Biomedical Research
Centre, was carried out as a multi-disciplinary collaboration
between Celsion, the Oxford University Institute of Biomedical
Engineering, the Oncology Clinical Trials Office (OCTO) and the
Oxford University Hospitals NHS Foundation Trust.
¹ For today’s news release issued by NIHR Oxford
Biomedical Research Centre regarding The Lancet Oncology
publication, please visit www.ox.ac.uk .
About ThermoDox®
Celsion’s most advanced program is a
heat-mediated, tumor-targeting drug delivery technology that
employs a novel heat-sensitive liposome engineered to address a
range of difficult-to-treat cancers. The first application of this
platform is ThermoDox®, a lyso-thermosensitive liposomal
doxorubicin (LTLD), whose novel mechanism of action delivers high
concentrations of doxorubicin to a region targeted with the
application of localized heat at 40°C, just above body temperature.
In one of its most advanced applications, ThermoDox®, when combined
with radiofrequency thermal ablation (RFA), has the potential to
address a range of cancers. For example, RFA in combination with
ThermoDox® has been shown to expand the “treatment zone” with a
margin of highly concentrated chemotherapy when treating individual
primary liver cancer lesions. The goal of this application is to
significantly improve efficacy.
Celsion’s LTLD technology leverages two
mechanisms of tumor biology to deliver higher concentrations of
drug directly to the tumor site. The first: Rapidly growing tumors
have leaky vasculature, which is permeable to liposomes and enables
their accumulation within tumors. Leaky vasculature influences a
number of factors within the tumor, including the access of
therapeutic agents to tumor cells. Administered intravenously, LTLD
is engineered to allow significant accumulation of liposomes at the
tumor site at the time of radiofrequency ablation as these
liposomes recirculate in the blood stream. The second: When the
tumor tissue is heated to a temperature of 40°C or greater, the
heat-sensitive liposome rapidly changes structure and the liposomal
membrane selectively dissolves, creating openings that release the
chemotherapeutic agent directly into the tumor and into the
surrounding vasculature. Drug concentration increases as a function
of the accumulation of liposomes at the tumor site, but only where
the heat is present. This method targets only the tumor and the
area related to tumor invasion, supporting precise drug
targeting.
About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll
up to 550 patients in up to 70 clinical sites in the United States,
Europe, China and Asia Pacific, and will evaluate ThermoDox® in
combination with optimized RFA, which will be standardized to a
minimum of 45 minutes across all investigators and clinical sites
for treating lesions three to seven centimeters, versus optimized
RFA alone. The primary endpoint for the trial is overall survival,
which is supported by post-hoc analyses of data from the Company's
701-patient HEAT Study, where optimized RFA has demonstrated the
potential to significantly improve survival when combined with
ThermoDox®. The statistical plan calls for two interim efficacy
analyses by an independent Data Monitoring Committee.
About Celsion
Corporation
Celsion is a fully-integrated oncology company
focused on developing a portfolio of innovative cancer treatments,
including directed chemotherapies, immunotherapies and RNA- or
DNA-based therapies. The Company's lead program is ThermoDox®, a
proprietary heat-activated liposomal encapsulation of doxorubicin,
currently in Phase III development for the treatment of primary
liver cancer. The pipeline also includes GEN-1, a DNA-based
immunotherapy for the localized treatment of ovarian and brain
cancers. Celsion has two platform technologies for the
development of novel nucleic acid-based immunotherapies and other
anti-cancer DNA or RNA therapies. For more information on Celsion,
visit our website: http://www.celsion.com. (CLSN-LTSL/ThermoDox®
CLSN-Optima Study/HCC)
About the National Institute for
Health Research Oxford Biomedical Research Centre
The National Institute for Health Research
Oxford Biomedical Research Centre is based at the Oxford University
Hospitals NHS Foundation Trust and run in partnership with the
University of Oxford, funded by the National Institute for Health
Research (NIHR).
The NIHR improves the health and wealth of the
nation through research. Established by the Department of Health,
the
NIHR:•
funds high quality research to improve
health•
trains and supports health
researchers•
provides world-class research
facilities•
works with the life sciences industry and charities to benefit
all•
involves patients and the public at every step
For further information, visit the NIHR website
www.nihr.ac.uk.
Celsion wishes to inform readers that
forward-looking statements in this release are made pursuant to the
"safe harbor" provisions of the Private Securities Litigation
Reform Act of 1995. Readers are cautioned that such forward-looking
statements involve risks and uncertainties including, without
limitation, unforeseen changes in the course of research and
development activities and in clinical trials; the uncertainties of
and difficulties in analyzing interim clinical data; the
significant expense, time, and risk of failure of conducting
clinical trials; the need for Celsion to evaluate its future
development plans; possible acquisitions or licenses of other
technologies, assets or businesses; possible actions by customers,
suppliers, competitors, regulatory authorities; and other risks
detailed from time to time in Celsion's periodic reports and
prospectuses filed with the Securities and Exchange Commission.
Celsion assumes no obligation to update or supplement
forward-looking statements that become untrue because of subsequent
events, new information or otherwise.
ThermoDox® is a registered trademark of Celsion
Corporation.
####
Celsion Investor Contact
Jeffrey W. Church
Sr. Vice President and CFO
609-482-2455
jchurch@celsion.com
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