Celsion Announces Presentation of OVATION Study Findings at the ASCO 2017 Annual Meeting
June 05 2017 - 8:00AM
100% disease control rate and
86% objective response rate reported
Celsion Corporation (NASDAQ:CLSN), an oncology drug development
company, today provided an update on its OVATION Study, a Phase Ib
dose escalating clinical trial combining GEN-1, the Company's
DNA-based immunotherapy, with the standard of care for the
treatment of newly-diagnosed patients with advanced (stage III/IV)
ovarian cancer who will undergo neoadjuvant chemotherapy followed
by interval debulking surgery. GEN-1 is an IL-12 DNA plasmid
vector formulated as a nanoparticle in a non-viral delivery system
to cause the sustained local production and secretion of the
Interleukin-12 (IL-12) protein loco-regionally at the tumor
site.
The Company announced the latest clinical and
translational data from the OVATION Study in a poster presentation
at the American Society of Clinical Oncology (ASCO) 2017 Annual
Meeting at McCormick Place in Chicago, IL. The poster
presentation, entitled "Phase 1 study of the safety and activity of
formulated IL-12 plasmid administered intraperitoneally in
combination with neoadjuvant chemotherapy in patients with newly
diagnosed advanced stage ovarian cancer," was presented on
Saturday, June 3rd from 1:15 PM to 4:45 PM by Dr. Premal H. Thaker,
Associate Professor, Obstetrics and Gynecology Division of
Gynecologic Oncology, Washington University in St. Louis School of
Medicine. The presentation summarized clinical findings and
available translational data from all fourteen patients treated in
the trial to-date.
“The OVATION study has accrued patients from
four major research cancer centers. We have seen highly
promising clinical findings including a patient with a
complete pathological response along with a very high rate of R0 at
time of debulking surgery. The translational research data in
the poster presentation demonstrates that GEN-1 is producing
beneficial cytokines and positively impacting T-cells in the
tumor,” said Dr. Premal Thaker. “This is strong early data and
we believe that GEN-1 may be stimulating the immune system to
improve tumor control in these patients. I am looking forward to
continuing our clinical evaluation of GEN-1 in subsequent ovarian
cancer studies.”
Celsion reported encouraging clinical data from
the first fourteen patients who have completed treatment in the
OVATION Study. GEN-1 plus standard chemotherapy produced
positive results, with no dose limiting toxicities and promising
dose dependent efficacy signals which appear to correlate well with
successful surgical outcomes as summarized below:
- Of the fourteen patients treated to date in the entire study,
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 microscopically 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.
- One patient demonstrated a pathological complete response
(pCR). pCRs are typically seen in less than 7% of patients
receiving neoadjuvant chemotherapy followed by surgical resection,
and have been associated with a median overall survival (OS) of 72
months, which is more than three years longer than those who do not
experience a pCR.
- All patients experienced a clinically significant decrease 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.
Celsion also reported supportive translational
research data from the first four patient cohorts who have
completed treatment in the OVATION Study. The translational
data provides further insight into GEN-1's mechanism of action
through the evaluation of dose-related changes in the tumor and
peritoneal immune cell population, as well as through the
peritoneal cytokine levels.
Treatment-Related Changes in IL-12 and Cytokine
Levels in Peritoneal Fluid
- 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, 79 mg/m2) and standard NACT
(carboplatin every 21 days and Taxol weekly) shows clear evidence
of IL-12 gene transfer and biological response following GEN-1
treatment on a dose-dependent basis.
- The translational data also demonstrated significant increases
in IFN-gamma 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.
Treatment-Related Changes in the Density of
Various T-cells in Tumors
- The immuno-histochemical (IHC) analysis of tumor tissue
collected before treatment (laparoscopy) and after completion of
eight GEN-1 weekly treatments showed increased infiltration of
CD3+, CD4+ CD8+ T-cells into tumor tissue of several
patients. The most pronounced effects observed in the IHC
analysis were decreases in the density of immunosuppressive T-cell
signals (FoxP3+, PD-1+, PDL-1+, IDO-1+) in the tumor
microenvironment. The ratio of CD8+ cells to
immunosuppressive T-cells was increased in 60-80% of patients
suggesting an overall shift in the immune environment to pro-immune
stimulatory following treatment with GEN-1.
- An intriguing effect of the treatment on tumor microenvironment
is a substantial reduction in the immunosuppressive T-cell subsets
and an overall shift in the T-cell environment to favoring immune
stimulation.
"Now having completed enrollment, per protocol,
of our OVATION Study, we are impressed with GEN-1’s apparent
activity in combination with standard chemotherapy in newly
diagnosed patients with stage III and IV ovarian cancer.
These data appear to correlate with the notable, unexpected
surgical outcomes among all patients completing the prescribed
eight weekly treatments and reinforce our confidence in the promise
of GEN-1’s ability to work safely and effectively in advanced
ovarian cancer," said Michael H. Tardugno, Celsion's chairman,
president and CEO. “Given these encouraging findings, in addition
to our plans to evaluate GEN-1 in combination with Avastin® in 2nd
line, the Company will consider continuing our clinical trials in
the underserved newly diagnosed patient population.”
OVATION Study Design
The Phase Ib trial evaluated weekly
intraperitoneal dosing of GEN-1 in combination with neoadjuvant
chemotherapy, the standard of care for patients newly diagnosed
with ovarian cancer. Concurrently with neoadjuvant chemotherapy,
enrolled patients received escalating weekly doses of GEN-1, from
levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly
for 8 treatments in total, followed by interval debulking surgery.
The regimen is primarily being evaluated for its safety and
tolerability.
About GEN-1 Immunotherapy
GEN-1, designed using Celsion's proprietary
TheraPlas platform technology, is an IL-12 DNA plasmid vector
encased in a nanoparticle delivery system, which enables cell
transfection followed by persistent, local secretion of the IL-12
protein. IL-12 is one of the most active cytokines for the
induction of potent anti-cancer immunity acting through the
induction of T-lymphocyte and natural killer (NK) cell
proliferation. The Company has previously reported positive safety
and encouraging Phase I results with GEN-1 given as monotherapy in
patients with peritoneally metastasized ovarian cancer, and
recently completed a Phase Ib trial of GEN-1 in combination with
PEGylated doxorubicin in patients with platinum-resistant ovarian
cancer.
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 anti-cancer DNA or RNA
therapies. 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 OVATION
Study 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, particularly for Phase I trials such as
the OVATION Study; 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.
Celsion Investor Contact
Jeffrey W. Church
Sr. Vice President and CFO
609-482-2455
jchurch@celsion.com
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