Celsion Announces Completion of OVATION Study and Provides Update on its Immunotherapy Trial in Advanced Stage III and IV Ova...
July 05 2017 - 8:00AM
86% Objective Response Rate (ORR) in Phase IB
Dose Escalating Study
Celsion Corporation (NASDAQ:CLSN) today provided an update on
its Phase Ib dose escalating clinical trial (the OVATION Study)
combining GEN-1, the Company's IL-12 gene-mediated immunotherapy,
with neoadjuvant chemotherapy for the treatment of newly-diagnosed
patients with Stage III and IV ovarian cancer followed by interval
debulking surgery.
Enrollment Complete in the OVATION
Study. The last patient in the 4th dose cohort has
completed their GEN-1 treatment which allows for a safety
evaluation by the Company’s Data Safety Monitoring Board (DSMB) in
mid-July. The Company recently announced the latest clinical
findings from the OVATION Study in a poster presentation at the
American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.
The presentation summarized clinical findings and translational
data from 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.
“We have seen promising clinical findings
including objective responses (CR and PR) in all patients at the
highest dose cohort along with an 87.5% rate of R0
(margin-negative) resections in the two highest dose cohorts and a
100% rate of R0 resections in the highest dose cohort at time of
debulking surgery. Additionally, translational research data
presented at ASCO demonstrates that GEN-1 is biologically active,
producing beneficial cytokines and positively impacting T-cell
population in the tumor,” said Dr. Nicolas Borys, Celsion’s senior
vice president and chief medical officer. “We believe that GEN-1
may be stimulating the immune system to improve tumor control in
these patients. We are currently evaluating the most cost-effective
development program to continue our clinical evaluation of GEN-1 in
subsequent ovarian cancer studies.”
Final translational research data for all
patients on the study is being collected and will be available in
the third quarter for evaluation by the Company’s Scientific
Advisory Committee and leading experts from Roswell Park,
Vanderbilt University, Washington University School of Medicine in
St. Louis, University of Alabama, Medical College of Wisconsin and
the University of Oklahoma. Previously reported preliminary
translational research findings from the first four patient cohorts
are summarized below:
- 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 by significant dose dependent increases in
IL-12 levels and 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 circulation.
- The immuno-histochemical (IHC) analysis of tumor tissue
collected before treatment (laparoscopy) and at debulking surgery
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 cells was increased in approximately 75% of
patients suggesting an overall shift in the immune environment to
pro-immune stimulatory following treatment with GEN-1. An
increase in CD8+ to immunosuppressive T-cell populations is
believed to be a good predictor of better overall survival.
“These translational research findings
demonstrate that GEN-1 in ovarian cancer patients is biologically
active and creates an immuno-stimulatory cytokine milieu in the
peritoneal cavity in a dose-dependent manner and promotes a
pro-immune T-cell population dynamic in the tumor
micro-environment,” said Dr. Khursheed Anwer, Celsion’s executive
vice president and chief science officer. “These distinct
immunological changes in 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.”
Progression Free Survival
Update. 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 who undergo neoadjuvant chemotherapy
followed by interval debulking surgery¹. Of the remaining six
patients who have been on the study for over one year, their
average PFS is 15 months with the longest progression-free patient
at 21 months. None of the patients in the third or fourth
dose cohorts have progressed to date.
“This progression-free survival trend adds to
the impressive clinical findings seen across a number of meaningful
measures used to assess ovarian cancer like an overall 86%
objective tumor response rate and a greater than 60% R0
(margin-negative) surgical resection rate,” said Michael H.
Tardugno, Celsion’s chairman, president and chief executive
officer. “The consistency and robust nature of the data across all
four cohorts and the encouraging clinical responses underscore the
potential of GEN-1 to serve as an effective, safe IL-12
immunotherapy in ovarian cancer.”
Manufacturing Technology Transfer for
GEN-1. In order to support the future clinical
development and global market strategy of GEN-1 in ovarian cancer,
the Company initiated a Technology Transfer, Manufacturing and
Commercial Supply Agreement (the “GEN-1 Agreement”) with a premier,
global API manufacturer, Zhejiang Hisun Pharmaceutical Co. Ltd.
(Hisun), in the second half of 2016. Hisun and Celsion have
completed several important technology transfer activities relating
to the manufacture of GEN-1, including studies required by CFDA for
site approval. The GEN-1 Agreement was initiated to pursue an
expanded partnership for the technology transfer relating to the
clinical and commercial manufacture and supply of GEN-1 for the
greater China territory, with the option to expand into other
countries in the rest of the world after all necessary regulatory
approvals are in effect. The GEN-1 Agreement will help to support
supply for both ongoing and planned clinical studies.
Key provisions of the GEN-1 Agreement are as
follows:
- The GEN-1 Agreement has targeted unit costs for clinical
supplies of GEN-1 that are substantially competitive with the
Company’s current suppliers.
- Once approved, the cost structure for GEN-1 will support rapid
market adoption and significant gross margins across global
markets.
This strategy provides the Company with a high
quality, affordable, cost effective supply for all global
markets.
Publication Accepted. The
Company also reported that the manuscript for a previously
completed trial conducted by the Gynecologic Oncology Group in
recurrent ovarian cancer using Doxil® and GEN-1 has been accepted
for publication in Gynecologic Oncology. The manuscript
describes positive clinical results from this study as summarized
below:
- This study enrolled 16 patients with platinum-resistant ovarian
cancer and evaluated the safety, tolerability, biological activity
and efficacy of weekly intraperitoneal GEN-1 administered in
combination with Doxil®. Patients received Doxil® on day 1 and
GEN-1 on days 1, 8, 15 and 22. Cycles were repeated every 28
days until unacceptable toxicity or disease progression.
- GEN-1 was well tolerated, with no dose limiting toxicities and
no overlapping toxicities between GEN-1 and Doxil®.
- The clinical findings demonstrated an overall clinical benefit
of 57% for all treatment arms, with a partial response (PR) rate of
21% and a stable disease (SD) rate of 36%. The overall clinical
benefit observed at the highest dose cohort in this
difficult-to-treat patient population was 86%.
Recurrent, platinum resistant ovarian cancer
patients have a poor prognosis. With these data along with other
published, pre-clinical data, the Company considers this group to
be a promising future population for a study of GEN-1 in
combination with Avastin® and Doxil®.
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 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 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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