Celsion Reports Data Safety Monitoring Board Recommendation to Proceed to Phase II of the OVATION 2 Study in Advanced Ovaria...
May 29 2020 - 8:30AM
Celsion Corporation (NASDAQ: CLSN), a leading oncology drug
development company, today announced the final recommendations of
the Data Safety Monitoring Board (DSMB) following completion of the
Phase I dose-finding and tolerance portion of the Phase I/II
OVATION 2 Study with GEN-1 in advanced (Stage III/IV) ovarian
cancer. Based on favorable safety data from 15 randomized patients,
the DSMB has recommended that the Phase II portion of the OVATION
Study proceed with the dose of 100 mg/m2. The DSMB also determined
that safety is satisfactory with an acceptable risk/benefit, and
that patients tolerate up to 17 doses of GEN-1 during a course of
treatment that lasts up to six months. No dose limiting toxicities
were reported.
The OVATION 2 Study combines GEN-1, the
Company's IL-12 gene-mediated immunotherapy, with standard-of-care
neoadjuvant chemotherapy (NACT) in patients newly diagnosed with
Stage III/IV ovarian cancer. NACT is designed to shrink the cancer
as much as possible for optimal surgical removal after three cycles
of chemotherapy. Following NACT, patients undergo interval
debulking surgery (IDS), followed by three additional cycles of
chemotherapy in order to treat any remaining tumor after the
surgery.
The OVATION 2 Study is an open-label, 1-to-1
randomized trial, 80% powered to show the equivalent of a 33%
improvement in progression-free survival (PFS) (HR=0.75), the
primary endpoint, when comparing the treatment arm (NACT + GEN-1)
with the control arm (NACT alone). GEN-1 is a formulation of
Celsion's proprietary, synthetic, non-viral cell transfection
platform TheraPlas, which incorporates DNA plasmids coded for the
inflammatory protein interleukin-12 (IL-12). Cell transfection is
followed by persistent, local secretion of the IL-12 protein at
therapeutic levels.
In March 2020, the Company announced the
following clinical data from these first 15 patients enrolled in
the OVATION 2 Study:
- Of the 15 patients treated in the
Phase I portion of the OVATION 2 Study:
- Nine were treated with GEN-1 at a dose of 100 mg/m² plus
NACT,
- Six were treated with NACT only,
- All 15 had successful resections of their tumors, with seven
out of nine patients (78%) in the GEN-1 treatment arm having a
complete tumor resection (R0), which indicates a microscopically
margin-negative resection in which no gross or microscopic tumor
remains in the tumor bed, and
- Only three out of six patients (50%) in the NACT only treatment
arm had an R0 resection.
- When combining these results with
the surgical resection rates observed in the Company’s prior Phase
Ib dose-escalation trial (the OVATION 1 Study), a population of
patients with inclusion criteria identical to the OVATION 2 Study,
the data reflect the strong dose-dependent efficacy of adding GEN-1
to the current standard of care NACT:
|
|
% Patients with R0 Resections |
0, 36, 47 mg/m² of GEN-1 plus NACT |
n=12 |
42% |
61, 79, 100 mg/m² of GEN-1 plus NACT |
n=17 |
82% |
- The objective response rate (ORR) as measured by Response
Evaluation Criteria in Solid Tumors (RECIST) criteria for the 0,
36, 47 mg/m² dose GEN-1 patients were comparable, as expected, to
the 61, 79, 100 mg/m² higher dose GEN-1 patients, with both groups
demonstrating an approximate 80% ORR.
The Company also engaged Medidata, a Dassault
Systèmes company, to examine matched patient data provided by
Medidata in a synthetic control arm (SCA) with results from the
Company’s completed Phase Ib dose-escalation OVATION 1 Study. The
results were announced in March 2020, and showed positive data in
PFS as follows:
GEN-1 Population |
PFS Hazard Ratio (Confidence Interval) |
Intent-to-treat, n=15 |
0.53 (95% CI 0.16, 1.73); log-rank p=0.29 |
Per-protocol, n=14 |
0.33 (95% CI 0.08, 1.37); log-rank p=0.11 |
Patients in the GEN-1 arm virtually demonstrated
a doubling of control of their cancer compared with the SCA.
Findings are not statistically significant due to the small number
of patients.
“These findings show a consistent dose dependent
clinical response in both surgical outcome and tumor response. This
is further supported by a series of translational data of the tumor
microenvironment,” noted Dr. Nicholas Borys, Celsion’s executive
vice president and chief medical officer. “Continuing our clinical
research program at the higher, 100mg/m2 dose, in this advance
stage ovarian cancer population, holds promise and is strongly
encouraged by our study investigators and medical advisors. We look
forward to initiating enrollment as quickly as possible.”
“We are excited to be moving into the Phase II
portion of the OVATION 2 Study, and thank the DSMB for their work
and advice,” said Michael H. Tardugno, Celsion’s chairman,
president and chief executive officer. “The recommendation to
proceed at the highest dose and the fact patients were able to
tolerate 17 doses bode well for study success, particularly in
light of the body of positive data we have generated for GEN-1 in
the advanced ovarian cancer indication. With no good treatment
options available, we are hopeful GEN-1 will make a meaningful
difference in the lives of these women. As previously announced, we
plan to begin the Phase II study in the fourth quarter of this
year.”
In March 2020, the Company announced that GEN-1
has received Orphan Drug Designation from the European Medicines
Agency. Celsion plans to consult with the U.S. Food and Drug to
request Fast Track review and potential Breakthrough Therapy
designation for GEN-1 based on this encouraging clinical data.
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 cancer.
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; 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
ContactJeffrey W. Church, EVP, CFO and Corporate
Secretary609-482-2455jchurch@celsion.com |
LHA Investor RelationsKim Sutton
Golodetz212-838-3777kgolodetz@lhai.com |
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