Celsion Announces Continuing Positive Data from the OVATION Study - An Immunotherapy Study of Newly Diagnosed Stage III and I...
November 10 2016 - 8:30AM
Third Cohort of Patients Continues to Show
Clinically Meaningful Responses in the Evaluation of GEN-1, A Novel
IL-12 DNA-based Immunotherapy, in Combination with the Standard of
Care
Celsion Corporation (NASDAQ:CLSN) today announced data from
the third cohort of patients in its Phase Ib dose escalating
clinical trial (the OVATION Study) combining GEN-1, the Company's
DNA-based immunotherapy, with the standard of care for the
treatment of newly-diagnosed patients with advanced ovarian cancer
who will undergo neoadjuvant chemotherapy followed by interval
debulking surgery. In the first nine patients dosed, GEN-1 plus
standard chemotherapy produced impressive results, with no dose
limiting toxicities and highly promising efficacy signals in this
difficult to treat cancer.
“While the patient number in this trial may be
small, the consistency and robust nature of the data across all
three cohorts and the encouraging clinical responses underscore the
potential of GEN-1 to serve as an effective, safe IL-12
immunotherapy in ovarian cancer,” said Nicholas Borys, M.D.,
Celsion's chief medical officer. “I am particularly impressed with
the pathological response data, which is known to be associated
with prolonged survival in this patient population. The data
generated support continued evaluation of GEN-1 in ovarian cancer,
and we look forward to seeing how GEN-1 performs in the fourth and
final study cohort.”
The OVATION Study is designed to enroll three to
six patients per dose cohort with the goal of identifying a safe,
tolerable and therapeutically active dose of GEN-1 by recruiting
and maximizing an immune response. The first three cohorts each
enrolled three patients. Enrollment in the fourth cohort is
ongoing, and Celsion expects to complete the OVATION Study this
year and report data in early 2017. Future studies of GEN-1 will
include a Phase I/II study combining GEN-1 with Avastin® and
Doxil®.
OVATION Study – Totality of Results in
the First Three Cohorts
- Of the first nine patients dosed, one patient demonstrated a
complete response (CR), five patients demonstrated partial response
(PR) and three patients demonstrated stable disease (SD), as
measured by RECIST criteria. This translates to a 100% disease
control rate (DCR), and 66% objective response rate (ORR).
- Eight patients had successful resections of their tumors, with
four patients having an R0 resection, which indicates a
microscopically margin-negative resection in which no gross or
microscopic tumor remains in the tumor bed, and three patients with
a R1 resection, indicating microscopic residual tumor. One patient
had an R2, indicating macroscopic residual tumor. One patient in
the second cohort was ineligible for debulking surgery due to a
medical complication unrelated to the study or the study drug.
- Of the eight surgically treated and evaluable patients, one
patient demonstrated a complete pathological response (cPR), three
patients demonstrated a micro pathological response (microPR), and
four patients demonstrated a macroPR. These data compare favorably
to historical data, which indicate that cPRs are typically seen in
less than 7% of patients receiving neoadjuvant chemotherapy
followed by surgical resection. cPRs have been associated with a
median overall survival of 72 months, which is more than three
years longer than those who do not experience a cPR. In addition,
microPRs are seen in approximately 30% of patients, and are
associated with a median overall survival of 38 months¹.
- Seven patients who completed treatment follow-up experienced a
dramatic (greater than 90%) drop in their CA-125 protein levels as
of their most recent study visit. CA-125 is used to monitor certain
cancers during and after treatment. CA-125 is present in greater
concentrations in ovarian cancer cells than in other cells. A 50%
reduction in CA-125 levels is considered meaningful. Six patients
maintained CA-125 levels below the standard cutoff level of 35
U/mL.
OVATION Study – Top Line Translational
Data from First Two Cohorts
Celsion also reported initial translational data
from the first two cohorts of the OVATION study. Tumor and blood
samples collected before the start of the neoadjuvant chemotherapy
(NACT) and after the completion of GEN-1 treatment at debulking
surgery are being analyzed for immune cell populations. Top line
data demonstrates intriguing immunological changes in the tumor
that are consistent with the activation of the immune system.
Specifically,
- In tumor tissue, there was an increase in cytotoxic CD8+ T-cell
density in three out of four evaluable patients at debulking
surgery. There was a decrease in immunosuppressive FoxP3+ T-cells
in two out of those 4 patients. The ratio of CD8+/FoxP3+ cells was
increased in all four evaluable patients. High tumor
infiltrating CD8+ T-cell density, low FoxP3+ T-cell density or high
CD8+/FoxP3+ ratio demonstrate a potential shift in tumor
environment to favoring immune stimulation following NACT + GEN-1
therapy. For the remaining two patients the post-treatment tumor
tissue was not available. In one of those two patients there was
complete pathological response hence no tumor tissue was present to
provide a post-treatment comparison. In the other patient the
debulking surgery was not performed due to disease related
complications.
- In plasma samples, there appeared to be no significant change
in T-cell density following the treatment. The density of myeloid
derived suppressor cells that are associated with immunosuppression
in ovarian cancer were either decreased or did not increase in
post-treatment samples.
Additional immune analysis of biological tissue
including cytokine ELISA from the first two patient cohorts and a
complete analysis of the two higher dose cohorts is in
progress.
“The clinical and translational data
generated to date are meaningful and reinforce our confidence in
the potential of GEN-1 to address advanced Stage III and IV ovarian
cancer, a population clearly in need of effective therapies,” said
Dr. Khursheed Anwer, Ph.D., MBA, Celsion's chief scientific
officer. “We anticipate completion of enrollment in the fourth
patient cohort in the coming weeks, and will continue to assess a
potential accelerated clinical development path for GEN-1. In
parallel, we are currently evaluating translational data from the
study, which we expect to report before the end of the fourth
quarter.”
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 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 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 customers, 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 Petrillo M, Zannoni GF, Tortorella L, et al.
Prognostic role and predictors of complete pathologic response to
neoadjuvant chemotherapy in primary unresectable ovarian cancer.
American Journal of Obstetrics & Gynecology 2014
Celsion Investor Contact
Jeffrey W. Church
Sr. Vice President and CFO
609-482-2455
jchurch@celsion.com
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