Celsion Announces Latest Translational Data from the OVATION Study in Newly Diagnosed Advanced Ovarian Cancer Patients
August 02 2017 - 8:00AM
Celsion Corporation (NASDAQ:CLSN) today announced findings
from the translational research data from its Phase Ib dose
escalating clinical trial (the OVATION Study) combining GEN-1, the
Company's IL-12 gene-mediated immunotherapy, with the standard of
care for the treatment of newly-diagnosed patients with Stage III
and IV ovarian cancer who will undergo neoadjuvant chemotherapy
(NACT) followed by interval debulking surgery.
Translational research data was reviewed with
leading immuno-oncology experts from the Roswell Park Cancer
Institute. The analysis of peritoneal fluid and blood samples
collected immediately before and 24 hours after IP administration
of multiple doses of GEN-1 (36, 47, 61, 72 mg/m2) and standard NACT
(carboplatin every 21 days and Taxol weekly) shows clear evidence
of IL-12 gene transfer by dose dependent increases in IL-12 levels
and immune system activity and significant increases in
interferon-gamma (IFN- γ) and decreases in VEGF levels. The
treatment-related changes in immune activating cytokines and
pro-tumor VEGF levels followed a dose-dependent trend and were
predominantly in the peritoneal fluid compartment with little to no
changes observed in the patients’ systemic blood stream.
Key translational research findings from the
first 12 of 15 patients¹ enrolled in four patient cohorts are
summarized below:
- The treatment-related changes in immune activating cytokines
and pro-tumor VEGF and IFN- γ levels followed a dose-dependent
trend and were predominantly in the peritoneal fluid compartment
with little to no changes observed in the patients’ systemic
circulation. The observed immunological changes are consistent with
an IL-12 based mechanism.
- Effects observed in the IHC analysis were pronounced decreases
in the density of immunosuppressive T-cell signals (FoxP3, PD-1,
PDL-1, IDO-1) and increases in CD8+ cells in the tumor
microenvironment.
- The ratio of CD8+ cells to immunosuppressive cells was
increased in approximately 75% of patients suggesting an overall
shift in the tumor microenvironment from immunosuppressive to
pro-immune stimulatory following treatment with GEN-1. An
increase in CD8+ to immunosuppressive T-cell populations is a
leading indicator and believed to be a good predictor of improved
overall survival.
“These translational research findings
demonstrate that GEN-1 in ovarian cancer patients is biologically
active and creates a shift in the tumor microenvironment in the
peritoneal cavity in a dose-dependent manner and promotes a
pro-immune T-cell population dynamic in the tumor
microenvironment,” said Dr. Khursheed Anwer, Celsion’s executive
vice president and chief science officer. “These distinct
immunological changes in the local disease environment appear to
translate into clinical benefit and warrant the continued
development of our GEN-1 IL-12 immunotherapy as a potential
adjuvant, in both first and second-line ovarian cancer.
Furthermore, pro-immune changes in the tumor microenvironment
appear to support research combining GEN-1 with other exciting
immuno-oncology therapies including adaptive T-cell and check point
inhibitors.”
The Company previously announced the latest
clinical findings from the OVATION Study in a poster presentation
at the American Society of Clinical Oncology (ASCO) 2017 Annual
Meeting in June 2017. The presentation summarized clinical
findings for all fourteen patients treated in the trial
to-date.
- Of the fourteen patients treated to date, two (2) patients
demonstrated a complete response, ten (10) patients demonstrated a
partial response and two (2) patients demonstrated stable disease,
as measured by RECIST criteria. This translates to a 100% disease
control rate (DCR) and an 86% objective response rate (ORR).
- Of the five patients treated in the highest dose cohort, there
was a 100% objective response rate with one (1) complete response
and four (4) partial responses.
- Fourteen patients had successful resections of their tumors,
with nine (9) patients (64%) having an R0 resection, which
indicates a margin-negative resection in which no gross or
microscopic tumor remains in the tumor bed.
- Of the five patients treated at the highest dose cohort, all
five patients (100%) experienced a R0 surgical resection.
Seven out of eight (87%) patients in the highest two dose cohorts
experienced a R0 surgical resection.
- Of the seven patients who have received GEN-1 treatment over
one year ago and are being followed, only one patient’s cancer has
progressed after 11.7 months. This compares favorably to the
historical median progression free survival (PFS) of 12 months for
newly-diagnosed patients with Stage III and IV ovarian cancer that
undergo neoadjuvant chemotherapy followed by interval debulking
surgery². Of the remaining six patients who have been on the
study for over one year, their average PFS is 16.4 months with the
longest progression-free patient at over 22 months.
“The impressive early trends in tumor response,
surgical resections and progression-free survival are consistent
with the dose dependent increases in IFN- γ levels, decreases in
VEGF levels and immune system activity observed in the
translational data,” said Michael H. Tardugno, Celsion's chairman,
president and chief executive officer. “Ovarian cancer patients
have a very poor prognosis. These data along with other published,
pre-clinical data, underscore the potential of GEN-1 to serve as an
effective, safe IL-12 immunotherapy in this underserved
population.”
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 and in Phase II development for the treatment of
recurrent chest wall breast cancer. The pipeline also includes
GEN-1, a gene-mediated 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 anticancer DNA or RNA therapies, including TheraPlas™ and
TheraSilence™. For more information on Celsion, visit our website:
http://www.celsion.com. (CLSN-G1 CLSN-OV)
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, particularly in small subgroups that are not statistically
significant; FDA and regulatory uncertainties and risks; 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 suppliers,
competitors, regulatory authorities; and other risks detailed from
time to time in the 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.
¹ Tissue samples are being collected and
translational data from the final three patients will be available
in late September 2017.
² Wright AA, Bohlke K, Armstrong DK, et al:
Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian
Cancer: Society of Gynecologic Oncology and American Society of
Clinical Oncology Clinical Practice Guideline. J Clin Oncol
34, 2016.
Celsion Investor Contact
Jeffrey W. Church
Sr. Vice President and CFO
609-482-2455
jchurch@celsion.com
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