Findings provide key validation; help identify target indications for
optimal
development
Data demonstrating safety and efficacy to be presented at
ASCO Annual Meeting
2015 on Sunday, May 31
PARIS & COPENHAGEN,
Denmark--(BUSINESS WIRE (http://www.businesswire.com/))--
Regulatory
News:
Onxeo S.A. (Paris:ONXEO) (NASDAQ OMX:ONXEO), an innovative company
specializing
in the development of orphan oncology drugs, today announced
preclinical &
clinical data from three studies supporting of the potential of
belinostat in
multiple orphan oncology indications, including results from its
Phase I/II
trial of belinostat in combination with standard chemotherapy in
patients with
soft tissue sarcomas (STS).
Judith Greciet, Chief Executive
Officer of Onxeo, said, “As a pan-HDAC
inhibitor, belinostat has shown
anti-tumor activity in several orphan oncology
diseases, and has the potential
to significantly enhance its value for the
Company. Results from our Phase I/II
study confirm that belinostat in
combination with chemotherapy was well
tolerated and, importantly, response
rates were observed in some patients with
advanced soft tissue sarcomas.
Furthermore, we show encouraging data from two
analyses of belinostat in
combination with chemotherapy in small cell lung
cancer and thymic epithelial
tumors that affirm this combination warrants
further evaluation in additional
orphan oncology indications. Collectively,
these data provide a key additional
information on belinostat at a time when
the Company is identifying new target
indications, and will help us optimally
advance the compound’s development.”
Results of the Phase I/II trial will be
presented during a poster session and
further reviewed during a separate poster
discussion session, both on Sunday,
May 31, at the 2015 American Society of
Clinical Oncology (ASCO)
Annual
Meeting (http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2F
am.asco.
org%2F&esheet=51112234&newsitemid=0&lan=en
-US&anchor=2015+American+Soc
iety+of+Clinical+Oncology+%28ASCO%29+Annual+Meeting&i
ndex=1&md5=9f60ab8f577dfc5
a42d1269ce8df7d5e),
being held May 29-June 2 in
Chicago, IL.
In addition, findings from the two
study analyses of belinostat are to be
published in conjunction with the Annual
Meeting.
Abstract 10516
(Poster
160) (http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fab
stracts.a
sco.org%2F156%2FAbstView_156_144405.html&esheet=51112234&newsitemid=0&
lan=en
-US&anchor=Abstract+10516+%28Poster+160%29&index=2&md5=dbc26d039da33848d9
31d4644d
7b3491) –
A phase I/II clinical trial of belinostat (PXD101) in combination
with
doxorubicin in patients with soft tissue sarcomas (STS).1
Lead author:
Joanna Vitfell-Rasmussen, M.D.,
University of
Copenhagen Herlev
Hospital
Poster Soft
Tissue
Session:
Date, Time, Sunday May 31, 8:00 – 11:30 a.m.
Location:
CDT; S Hall A, McCormick Place
Poster Sunday May 31, 4:30
– 5:45 p.m. CDT;
Discussion S404, McCormick Place
Session:
The
completed Phase I/II, open-label, multi-center, dose-escalation
study
(NCT00878800 (http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%
2F%2Fcl
inicaltrials.gov%2Fshow%2FNCT00878800&esheet=51112234&newsitemid=0&lan=e
n
-US&anchor=NCT00878800&index=3&md5=f02cd9fe5dd2f324b50d68fbae3e54ea))
evaluated
the safety and efficacy of belinostat in combination with standard
chemotherapy
doxorubicin in a total of 41 patients and found the combination
was well
-tolerated and exhibited anti-cancer activity in 12 of 20 patients
with advanced
soft tissue sarcomas at the maximum tolerated dose (MTD).
The
Phase I dose-escalation portion of the study assessed 25 patients with
advanced
solid tumors across four cohorts of increasing doses and found the MTD
to be
the highest tested dose level of 1000
mg/m2intravenously-administered
belinostat combined with 75
mg/m2 doxorubicin.
Common drug-related events included fatigue (95%), nausea
(76%) and alopecia, or
hair loss (63%), and one dose-limiting toxicity of Grade
3 rash was observed.
Dose-normalized area under the curve and maximum
concentration appeared
relatively consistent across the different cohorts,
indicating that belinostat
exhibited linear pharmacokinetics across the dose
range, and that doxorubicin
had no effect on belinostat exposure. Two patients
receiving the MTD exhibited
partial responses, for a response rate of 8% (95%
CI).
The Phase II portion, which assessed efficacy of the combination at MTD
in 20
patients with soft tissue sarcomas including four patients from the Phase
I
portion, demonstrated two patient responses, 9 patients with stable disease
and
a response rate of 13% (95% CI). Of the two responses, one patient had a
partial
response at cycle 4 of treatment and the second patient had a complete
response
at cycle 2. These two responses resulted in stopping of the trial
after
enrolling 20 patients, meeting a pre-determined stopping rule that the
Phase II
trial would be stopped if no more than 2 responses (complete or
partial) were
seen among the 20 patients within the first two treatment
cycles.
Abstract
e13581 (http://cts.businesswire.com/ct/CT?id=smartlink&url=htt
p%3A%2F%2Fabstracts
.asco.org%2F156%2FAbstView_156_146151.html&esheet=51112234&n
ewsitemid=0&lan=en
-US&anchor=Abstract+e13581&index=4&md5=0b0229b2b2d98e17d0a55d
5c22cc07bc) – UGT1A1
genotype
effects on PK, PD and toxicities of belinostat administered by 48 h
continuous
infusion.2
Lead Andrew K.L. Goey, Genitourinary Malignancies
Branch,
Author: Center for Cancer Research, National Cancer
Institute
Publication Pharmacology
Only:
This is the first study to
simultaneously evaluate the genotype effects of
UGT1A1, a gene that plays a
major role in the metabolism of belinostat, on the
drug interactions and
toxicities of belinostat in combination with other
chemotherapies.
In a Phase
I trial of 25 patients with small cell lung cancer and other cancers
of
neuroendocrine origin and in a separate Phase I/II trial of 26 patients
with
thymic epithelial tumors, belinostat was administered by 48-hour
continuous
infusion across various dose levels (400-1000 mg/m2 per 24 hours) in
combination
with either cisplatin and etoposide, or cisplatin, doxorubicin
and
cyclophosphamide, respectively. Patients in both trials were
genotyped
for UGT1A1 variants associated with reduced function.
The genotype
UGT1A1 was associated with systemic exposure to belinostat and with
incidence
of toxicities in the Phase I trial, particularly at doses greater than
400
mg/m2 per 24 hours. The Phase I/II trial showed these associations to be
less
profound. Based on these results, genotype-based dose adjustments of
belinostat
may be desirable regardless of whether belinostat is used as a single
-agent or
in
combination.
Abstract e18564 (http://cts.businesswire.com/ct/CT?id=smartlink&ur
l=http%3A%2F%2F
abstracts.asco.org%2F156%2FAbstView_156_150189.html&esheet=51112
234&newsitemid=0&
lan=en-US&anchor=Abstract+e18564&index=5&md5=ed0c8c6e165e08da9
3ee6feb862a1c64) –
Effect
of treatment on the regression and growth rates of thymic epithelial
tumors
(TETs).3
Lead Mauricio Burotto, M.D., Center for Cancer
Research,
Author: National Cancer Institute, National Institutes
of Health
Publication Thymic Malignancies
Only:
The study used a
mathematical model to characterize the effect of different
therapies on the
rate of tumor regression and the rate of tumor growth while a
therapy is
administered in thymic epithelial tumors (TETs), rare tumors with
limited
treatment options and limited standard measures of tumor
response
evaluation.
The assessment included data from a total of 74 patients
across four trials: one
Phase I/II trial of belinostat in combination with
cisplatin, doxorubicin,
cyclophosphamide (NCT01100944) and three, single-agent
Phase II clinical trials
evaluating belinostat (NCT00589290), cixutumumab
(NCT00965250) or sunitinib
(NCT01621568).
The study showed rates of tumor
regression of belinostat combination treatment
were significantly higher
compared to the other three therapies, which implies a
clinically higher
objective response rate. However, there were no significant
differences in
tumor growth rate between the four therapies (p = 0.83),
indicating that while
belinostat with chemotherapy may be used as initial
therapy to render some
disease resectable, novel therapies that can slow tumor
growth and can be
tolerated for prolonged periods of time are needed to
significantly prolong
overall survival in TETs.
About Soft Tissue Sarcomas (STS)
Sarcomas are a
group of solid tumors in the connective tissue of the body that
are treated
with surgery, chemotherapy, and/or radiation. Reported objective
response rates
are very low with complete responses being rare or absent in the
trials that
have led to the registration of anti-cancer treatments in this
indication over
the past six years. Currently, doxorubicin as a single agent or
in combination
with ifosfamide is the most commonly used chemotherapeutic
regimen in patients
with advanced STS.
About Belinostat (Beleodaq®)
Belinostat is a novel histone
deacetylase (HDAC) inhibitor that has anti-cancer
activity associated with the
inhibition of cell proliferation, the induction of
apoptosis (programmed cell
death), the inhibition of angiogenesis and the
induction of cellular
differentiation.
Belinostat is designated as an orphan drug in Europe and the
United States. In
July 2014, belinostat (Beleodaq®) was granted accelerated
approval in the U.S.
by the Food and Drug Administration (FDA) for the
treatment of patients with
relapsed or refractory peripheral T-cell lymphoma
(PTCL) in 2nd-line treatment
after failure of standard chemotherapy. The
initiation of a Phase III trial in
collaboration with Onxeo’s U.S. partner,
Spectrum Pharmaceuticals, Inc. is
planned for the first half of 2016 to expand
the indication from 2nd to 1st line
treatment of PTCL.
Beyond PTCL,
belinostat’s clinical profile supports further development in new
and promising
orphan oncology indications. Onxeo is currently reviewing
potential indications
in order to define the optimal development plan for
belinostat.
About
Onxeo
Onxeo has the vision to become a global leader and pioneer in oncology,
with a
focus on orphan or rare cancers, through developing innovative
therapeutic
alternatives designed to “make the difference”. The Onxeo team is
determined to
develop innovative medicines that provide patients with hope and
significantly
improve their lives.
Key orphan oncology products at the
advanced development stage are:
Livatag® (doxorubicin Transdrug™): Phase III in
hepatocellular carcinoma
Validive® (clonidine Lauriad®): Phase II in severe
oral mucositis: Positive
preliminary top-line results
Beleodaq® (belinostat):
registered in the US in peripheral T-cell lymphoma
For more information, visit
the
website www.onxeo.com (http://cts.businesswire.com/ct/CT?id=smartlink&url=ht
tp%3A
%2F%2Fwww.onxeo.com&esheet=51112234&newsitemid=0&lan=en
-US&anchor=www.onx
eo.com&index=6&md5=d6701271563b6147527378e08396b659)
Disclaimer
This
communication expressly or implicitly contains certain
forward-looking
statements concerning Onxeo and its business. Such statements
involve certain
known and unknown risks, uncertainties and other factors, which
could cause the
actual results, financial condition, performance or
achievements of Onxeo to be
materially different from any future results,
performance or achievements
expressed or implied by such forward-looking
statements. Onxeo is providing this
communication as of this date and does not
undertake to update any forward
-looking statements contained herein as a
result of new information, future
events or otherwise. For a discussion of
risks and uncertainties which could
cause actual results, financial condition,
performance or achievements of Onxeo
to differ from those contained in the
forward-looking statements, please refer
to the Risk Factors ("Facteurs de
Risque") section of the 2014 Reference
Document filed with the AMF on April 14,
2015, which is available on the AMF
website
(http://www.amf
-france.org (http://cts.businesswire.com/ct/CT?id=smartlink&url=
http%3A%2F%2Fwww.
amf-france.org&esheet=51112234&newsitemid=0&lan=en
-US&anchor=
http%3A%2F%2Fwww.amf
-france.org&index=7&md5=8d5b524fa44779e94fea59823225f51d))
or on the
company’s
website
(www.onxeo.com (http://cts.businesswire.com/ct/CT?id=smartlink
&url=http%3A%2F%2Fw
ww.onxeo.com&esheet=51112234&newsitemid=0&lan=en
-US&anchor=
www.onxeo.com&index=8&md5=56ac4dd370003de8abb2f8e72e071702)).
References
1.
Vitfell-Rasmussen, J. et al. J Clin Oncol 33, 2015 (suppl; abstract 10516)
2.
Goey, A. et al. J Clin Oncol 33, 2015 (suppl; abstract e13581)
3. Burotto, M.
et al. J Clin Oncol 33, 2015 (suppl; abstr e18564)
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Onxeo S.A.
Judith Greciet,
CEO
j.greciet@onxeo.com
Nicolas Fellmann, CFO
n.fellmann@onxeo.com
+33 1 45 58
76 00
or
Europe
Alize RP
onxeo@alizerp.com
Caroline Carmagnol
+33 6 64 18 99
59
or
U.S.
The Ruth Group
Lee Roth (investors)
lroth@theruthgroup.com
(646)
536-7012
Kirsten Thomas (media)
kthomas@theruthgroup.com
(646) 536-7014
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