Celsion Announces Final Clinical and Translational Research Data from its OVATION Study at the AACR Special Conference on Ova...
October 03 2017 - 9:00AM
100% Disease Control; 86% Objective Response Rate
and 86% R0 & R1 Surgical Resection Rate in All Patients Treated
in Four Dose-Escalating Cohorts
Celsion Corporation (NASDAQ:CLSN), an oncology drug development
company, today announced final clinical and translational research
data from 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 to the tumor
site.
The Company updated the translational data from
the OVATION Study in a poster presentation at the American
Association of Cancer Research (AACR) Special Conference entitled
“Addressing Critical Questions in Ovarian Cancer Research and
Treatment” at the Wyndham Grand Pittsburgh Downtown in Pittsburgh,
PA. The poster entitled "Immunological changes following
intraperitoneal administration of a formulated IL-12 plasmid in
combination with neoadjuvant chemotherapy in newly diagnosed
advanced ovarian cancer patients," was presented by Dr. Khursheed
Anwer, Celsion’s executive vice president and chief scientific
officer in a poster session on Monday, October 2, 2017 from 6:00 PM
to 8:30 PM.
The Company also held an Advisory Board Meeting
on September 27, 2017 with the clinical investigators and
scientific experts including those from Roswell Park Cancer
Institute, Vanderbilt University Medical School, and M.D. Anderson
Cancer Center to review and finalize clinical, translational
research and safety data from the OVATION Study in order to
determine the next steps forward for this exciting new
immunotherapy. With the endorsement and recommendations from
the Advisory Board, the Company expects to file a next phase
protocol with FDA later this year.
Translational Research Data
Key translational research findings from all
evaluable patients are consistent with the earlier reports from
partial analysis of the data and are summarized below:
- The intraperitoneal treatment of GEN-1 in conjunction with
neoadjuvant chemotherapy resulted in dose dependent increases in
IL-12 and Interferon-gamma (IFN-g) levels that were predominantly
in the peritoneal fluid compartment with little to no changes
observed in the patients' systemic circulation. These and other
post-treatment changes including decreases in VEGF levels in
peritoneal fluid are consistent with an IL-12 based immune
mechanism.
- Consistent with the previous partial reports, the 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.
- Analysis of peritoneal fluid by cell sorting, not reported
before, shows treatment-related decrease in the percentage of
immunosuppressive T-cell (Foxp3+), which is consistent with the
reduction of Foxp3+ T-cells in the primary tumor tissue, and a
shift in tumor naïve CD8+ cell population to more efficient tumor
killing memory effector CD8+ cells.
These translational research findings
demonstrate that GEN-1 in ovarian cancer patients is biologically
active and creates a shift in the primary tumor and in the
surrounding tumor environment in the peritoneal cavity that
promotes a pro-immune T-cell population dynamic and conversion of
tumor naïve T-cell into cytotoxic effector T-cells in the tumor
microenvironment.
"These distinct immunological changes in the
local disease environment are likely 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,” said Dr. Kunle
Odunsi, Deputy Director, Chair of Gynecologic Oncology and
Center for Immunotherapy Executive Director at Roswell Park Cancer
Institute. “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."
Clinical Data
Celsion also reported highly encouraging
clinical data from the first fourteen patients who have completed
treatment in the OVATION Study. GEN-1 plus standard
chemotherapy produced positive clinical results, with no dose
limiting toxicities and promising dose dependent efficacy signals
which correlate well with successful surgical outcomes as
summarized below:
- Of the fourteen patients treated 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.
Seven out of eight (87%) patients in the highest two dose cohorts
experienced a R0 surgical resection. All five patients treated at
the highest dose cohort experienced a R0 surgical resection.
- 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.
- Of the eight patients who have received GEN-1 treatment over
one year ago (cohort 1 – 3) and are being followed; only two
patients’ cancer has progressed. 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 surgery. Of the remaining six patients who have
been on the study for over one year, their average PFS as of
September 30, 2017 is 18 months with the longest progression-free
patient at 24 months.
"We have completed enrollment of our Phase Ib
OVATION Study in newly diagnosed ovarian cancer patients to
determine GEN-1’s clinical and biological activity in combination
with standard chemotherapy. The remarkable surgical outcomes
for all patients completing the prescribed eight weekly treatments
of GEN-1 reinforce our belief in the promise of GEN-1’s ability to
work safely and effectively in advanced ovarian cancer," said Dr.
Nicholas Borys, Celsion's senior vice president and chief medical
officer. “The Advisory Board Meetings held in late September 2017
with our clinical investigators and scientific experts in
immuno-oncology provided an important endorsement of our
development program for this innovative immunotherapy for first
line ovarian cancer."
The poster presentation will be available on
Celsion’s website under “News & Investors – Scientific
Presentations.”
OVATION Study Design
The Phase Ib trial was designed to evaluate
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 will receive 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, with interval
debulking surgery to follow. The regimen will primarily be
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. 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 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 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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