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%2Fam.asco
.
org%2F&esheet=51112234&newsitemid=0&lan=en
-US&anchor=2015+American+Society+of+Clinical+Oncology+%28ASCO%29+Annual+Meeting&
i
ndex=1&md5=9f60ab8f577dfc5a42d1269ce8df7d5e), 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%2Fabstracts.
a
sco.org%2F156%2FAbstView_156_144405.html&esheet=51112234&newsitemid=0&lan=en
-US&anchor=Abstract+10516+%28Poster+160%29&index=2&md5=dbc26d039da33848d931d4644
d
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%2Fc
l
inicaltrials.gov%2Fshow%2FNCT00878800&esheet=51112234&newsitemid=0&lan=en
-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=http%3A%2F%2Fabstract
s
.asco.org%2F156%2FAbstView_156_146151.html&esheet=51112234&newsitemid=0&lan=en
-US&anchor=Abstract+e13581&index=4&md5=0b0229b2b2d98e17d0a55d5c22cc07bc) – UGT1A
1
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&url=http%3A%2F%2
F
abstracts.asco.org%2F156%2FAbstView_156_150189.html&esheet=51112234&newsitemid=0
&
lan=en-US&anchor=Abstract+e18564&index=5&md5=ed0c8c6e165e08da93ee6feb862a1c64) –
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=http%3
A
%2F%2Fwww.onxeo.com&esheet=51112234&newsitemid=0&lan=en
-US&anchor=www.onxeo.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%2F
w
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)
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(646) 536-7012
Kirsten Thomas (media)
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(646) 536-7014
Onxeo Announces Preclinical & Clinical Data from Three Studies Supporting the Potential For Belinostat in Multiple Orphan Oncology Indications
| Source: Onxeo SA
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