DGAP-News: Press Release: 4SC to present additional safety and efficacy data for cancer drug Resminostat from its Phase II SHELTER trial in liver cancer
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Press Release: 4SC to present additional safety and efficacy data for
cancer drug Resminostat from its Phase II SHELTER trial in liver
cancer
28.06.2012 / 07:30
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Press Release
4SC to present additional safety and efficacy data for cancer drug
Resminostat from its Phase II SHELTER trial in liver cancer at ESMO GI
Cancer Meeting
Planegg-Martinsried, Germany - 28 June 2012 - 4SC AG (Frankfurt, Prime
Standard: VSC), a biopharmaceutical company dedicated to the discovery and
development of targeted small molecule drugs for autoimmune diseases and
cancer, will today present Phase II data on safety, tolerability and
efficacy of the cancer drug resminostat as a second line therapy for liver
cancer at the 14th World Congress of Gastrointestinal Cancer of the
European Society for Medical Oncology (ESMO GI meeting) in Barcelona,
Spain, from 27-30 June 2012. The Phase II SHELTER study enrolled patients
with advanced liver cancer (hepatocellular carcinoma, HCC) who had
exhibited radiologically proven tumour progression under first-line therapy
with sorafenib (Nexavar(R)), the only drug currently approved for this
indication. The study evaluated resminostat in combination with sorafenib
and as single agent in monotherapy.
Professor Dr. Tom Ganten, principal investigator of the SHELTER trial at
the Heidelberg University Hospital, Germany, will present the data in a
poster session today, Thursday, 28 June 2012, from 10:50-11:20 am and from
4:15-4:30 pm (CEDT). The poster presentation will report new data from the
dose escalation part of the study and also additional data on the clinical
efficacy of resminostat, including an analysis of the mean treatment
durations (TD) in both study arms.
Dose escalation
Data from three study groups (i.e. dose levels, DL) combining increasing
doses of resminostat [DL1: 200 mg (n=3), DL2: 400mg (n=3) and DL3: 600mg
(n=6)] with a total daily dose of 400 mg sorafenib and a fourth study group
(DL4) combining the highest resminostat dose of 600 mg with the approved
maximal dose of 800 mg sorafenib (n=6) will be reported. The combination of
resminostat and sorafenib was generally well tolerated at all dose levels,
and no DLT (dose limiting toxicity) was recorded at the highest doses in
DL4, thus a formal MTD (maximum tolerated dose) was not established in the
trial. These findings open the opportunity also for a potential 1st line
development of resminostat in combination with sorafenib with the goal of
improving the only existing single agent therapy sorafenib for 1st line
advanced HCC patients by combination with resminostat.
Efficacy data
The reported mean treatment durations in both study arms are currently
calculated at 2.5 months for patients treated with resminostat alone and at
5.5 months for patients treated with the combination of resminostat and
sorafenib. These values are still preliminary since in both trial groups a
number of patients are still active on study treatment. Furthermore, a
pair-wise comparison of 1st line sorafenib treatment durations prior to
entry into the SHELTER trial and the treatment durations patients obtained
in the 2nd line setting during the SHELTER trial are presented. In both
study arms subsets of patients were treated longer in 2nd line compared to
their 1st line therapy. Notably, this effect was more pronounced in the
combination group, indicating that the combination therapy of resminostat
and sorafenib was particularly able to stabilise the tumour disease. In
addition, as an update on the primary efficacy endpoint of the SHELTER
trial, the progression-free survival rates (PFSR) after 12 weeks of
treatment are provided. In the monotherapy group this PFSR by today is
calculated at 40% (not the final value since some patients are awaiting
staging at week 12 of treatment); in the combination group the final PFSR
is 70% as reported previously.
Dr. Bernd Hentsch, Chief Development Officer of 4SC AG, commented: 'The new
data reported for the dose escalation part of the SHELTER study show that
resminostat can also be combined safely with the 800 mg dose of sorafenib,
which is approved and routinely applied in 1st line therapy of advanced HCC
patients. Furthermore, it is encouraging to see that a number of patients
were treated longer in the 2nd line setting of the SHELTER study
particularly with the combination of resminostat and sorafenib than with
sorafenib alone during their 1st line therapy. This now offers the
additional opportunity to investigate the combination of resminostat and
sorafenib also in a 1st line setting for HCC, serving the continued high
medical need for new therapeutic options in this advanced disease stage.'
The efficacy data of the SHELTER study evaluating resminostat both in
monotherapy and in combination with sorafenib in patients with advanced HCC
showing tumour progression on 1st line sorafenib therapy, was presented at
this year's Annual Meeting of the American Society of Clinical Oncology
(ASCO) on 4 June 2012 in Chicago (USA). The data of the
resminostat/sorafenib combination therapy showed a progression-free
survival rate (PFSR) after 12 weeks of 70% and a median progression-free
survival (PFS) of 4.7 months. For the monotherapy group, the
progression-free survival rate (PFSR) at 12 weeks is now calculated at 40%
based on the current data analysis, and median PFS is currently expected to
be finally in the range of 2.0-2.5 months. As previously reported, the
primary study endpoint PFSR at 12 weeks had been achieved ahead of schedule
in both the combination and the monotherapy group.
From 28 June 2012, 10:50 am (CEDT), the poster presented at the ESMO GI
meeting can be downloaded at
http://www.4sc.de/product-pipeline/publications-posters/resminostat.
Ends
Details of the Presentation:
Presentation/Poster No. P-0082
Title: 'Dose Escalation of the HDAC Inhibitor Resminostat in Combination
Treatment with Sorafenib in Patients with Hepatocellular Carcinoma - The
Phase I/II SHELTER study'
Session date and time: Thursday, 28 June 2012, 10:50-11.20 am and 4:15-4:30
pm (CEDT)
Authors/Presenters: T. M. Ganten1, M.A. Woerns2, J. Siveke3, M.M.
Dollinger4, M.E. Scheulen5, H. Wege6, A. Mais7, B. Hauns7, S.W. Henning7,
B. Hentsch7, M. Horger8, U.M. Lauer9, M. Bitzer9, SHELTER Study Group
1 Department of Internal Medicine, University of Heidelberg, Heidelberg,
Germany,
2 Medical University Clinic, Mainz, Germany,
3 Medical Department II, University Hospital Rechts der Isar, Munich,
Germany,
4 Department of Internal Medicine, University of Halle, Halle, Germany,
5 West German Cancer Center, University Hospital, Essen, Germany
6 Medical University Clinic, Hamburg-Eppendorf, Germany
7 4SC AG, Planegg-Martinsried, Germany
8 Diagnostic Radiology, University of Tuebingen, Tuebingen, Germany
9 Medical University Clinic, Tuebingen, Germany,
About the SHELTER Trial Design
The two-arm, international Phase II SHELTER study evaluates resminostat as
a second-line treatment of patients with advanced liver cancer (HCC), alone
or in combination with sorafenib (Nexavar(R)), the current standard of care
in the first-linetreatment of advanced HCC, to see if it can prolong
progression-free survival (PFS) in patients who developed progressive
disease under first-line treatment with sorafenib. In the first study arm,
patients are being treated with the recommended dose of the combination
therapy (600 mg resminostat (OD) and 400 mg sorafenib (BID)) which was
determined through an initial dose-escalation part of the study. In the
second study arm, patients receive resminostat as monotherapy, administered
orally, once daily, over five consecutive days, followed by a nine day
treatment-free period (5+9 dosing schedule). In the combination arm,
resminostat is administered in the same 5+9 dosing schedule, while
sorafenib is administered daily throughout the cycle. In both study arms,
this 14-day-cycle is repeated until there is evidence of progressive
disease or until the patient leaves the study for other reasons. The first
two radiological tumour stagings are performed after six and 12 weeks;
after that, tumour stagings are performed every eight weeks. Patients who
experience a clinical benefit, e.g. a stabilization of their progressive
disease or tumour regression, may continue the study treatment. It was the
primary study objective to halt the further progression of this
particularly aggressive cancer disease in at least 20% of the patients
treated and for at least 12 weeks in both therapy arms. The primary
endpoint of the study is to determine the progression free survival rate
(PFSR) after 12 weeks of treatment. Secondary endpoints include the
analysis of time-to-progression (TTP), progression-free survival time
(PFS), overall survival (OS), drug safety and tolerability,
pharmacokinetics and the investigation of biomarkers.
About Liver Cancer (Hepatocellular Carcinoma, HCC)
Hepatocellular carcinoma (HCC) is the most frequent form of liver cancer.
Liver cancer is the fifth most common cancer worldwide and, with
approximately 700,000 deaths annually, the third most deadly. The incidence
of HCC is particularly high in Pacific-Asia and Southern Europe. The
aetiology of the disease varies between different areas. In Asia, hepatitis
B virus (HBV) infection is the major risk factor for HCC, whereas in the
Western world, hepatitis C virus (HCV) infection and alcohol abuse are the
most frequent cause for liver cirrhosis, and subsequently, HCC. Even though
over the past 10 years advancements in diagnosis and treatment of HCC have
lead to certain improvements in the prognosis for HCC patients, the
treatment options for patients with advanced HCC are still very poor. With
sorafenib (Nexavar(R)), there is currently only one compound approved for
this patient group. With a five-year survival rate of less than 10%,
advanced HCC has one of the lowest overall survival rates of all cancer
diseases worldwide. Thus, particularly for these patients with advanced
HCC, there is still a high unmet medical need for novel, systemic therapy
options, especially for patients refractory or intolerant to sorafenib.
About Resminostat
Resminostat (4SC-201), 4SC's lead oncology compound, is an oral
pan-histone-deacetylase (HDAC) inhibitor with an innovative epigenetic
mechanism of action that potentially enables the compound to be deployed as
a novel, targeted tumour therapy for a broad spectrum of oncological
indications, both as a monotherapy and in combination with other cancer
drugs. HDAC inhibitors have been shown to modify the DNA structure of
tumour cells to cause their differentiation and programmed cell death
(apoptosis) and are therefore considered to offer a mechanism of action
that has the particular potential to halt tumour progression and induce
tumour regression. Additionally, resminostat is also assumed to induce what
is known as tumour cell 'sensitisation' to other anti-cancer compounds.
This process can suppress or reverse certain tolerance mechanisms which
tumour cells often develop against such cancer drugs. Supplementary
treatment with resminostat can be expected to restore or significantly
improve the efficacy of a previously administered cancer therapy which was
no longer effective; furthermore, combining resminostat and common cancer
drugs right from the very beginning can also be expected to effectively
enhance the success of such a treatment.
Resminostat is currently being investigated in a broad clinical Phase II
programme in the three indications liver cancer (hepatocellular carcinoma,
HCC), Hodgkin's Lymphoma (HL), and colorectal cancer (CRC). In the Phase II
SAPHIRE trial in patients with advanced Hodgkin's Lymphoma, resminostat in
monotherapy has demonstrated substantial anti-tumour activity, with an
overall response rate of 35.3% and a clinical benefit in 55.9% of the
patients in a heavily pre-treated patient population together with very
good safety and tolerability. In the Phase I/II SHORE study, which
evaluates resminostat in combination with the chemotherapeutic FOLFIRI
regimen as a second-line treatment of KRAS-mutant CRC patients, initial
results are expected in 2012. Furthermore, in the Phase II SHELTER study
resminostat is being evaluated as monotherapy and in combination with
sorafenib as a second-line treatment in advanced HCC after radiologically
proven disease progression under first-line sorafenib therapy. According to
the data presented at the ASCO annual meeting on 4 June 2012,
resminostat/sorafenib combination therapy showed a progression-free
survival rate (PFSR) after 12 weeks of 70.0% and a median PFS of 4.7
months. The primary study endpoint has been achieved ahead of schedule in
both the combination and the monotherapy group.
4SC is currently in discussions with regulatory agencies and potential
partners in order to prepare a pivotal clinical study programme for
resminostat in combination with sorafenib as a second-line treatment for
patients with advanced HCC who show tumour progression on first-line
treatment with sorafenib.
About 4SC
The Group managed by 4SC AG (ISIN DE0005753818) discovers and develops
targeted, small-molecule drugs for treating diseases with high unmet
medical needs in various autoimmune and cancer indications. These drugs are
intended to provide innovative treatment options that are more tolerable
and efficacious than existing therapies, and provide a better quality of
life. The Company's balanced pipeline comprises promising products that are
in various stages of clinical development. 4SC's aim is to generate future
growth and enhance its enterprise value by entering into partnerships with
leading pharmaceutical companies. Founded in 1997, 4SC had 90 employees at
31 March 2012. 4SC AG has been listed on the Prime Standard of the
Frankfurt Stock Exchange since December 2005.
Legal Note
This document may contain projections or estimates relating to plans and
objectives relating to our future operations, products, or services; future
financial results; or assumptions underlying or relating to any such
statements; each of which constitutes a forward-looking statement subject
to risks and uncertainties, many of which are beyond our control. Actual
results could differ materially, depending on a number of factors.
For more information please visit www.4sc.com or contact:
4SC AG
Jochen Orlowski, Corporate Communications&Investor Relations
jochen.orlowski(at)4sc.com, Tel.: +49 (0) 89 70 07 63 66
MC Services
Raimund Gabriel
raimund.gabriel(at)mc-services.eu, Tel.: +49 (0) 89 21 02 28 30
End of Corporate News
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Language: English
Company: 4SC AG
Am Klopferspitz 19a
82152 Martinsried
Germany
Phone: +49 (0)89 7007 63-0
Fax: +49 (0)89 7007 63-29
E-mail: public(at)4sc.com
Internet: www.4sc.de
ISIN: DE0005753818
WKN: 575381
Listed: Regulierter Markt in Frankfurt (Prime Standard);
Freiverkehr in Berlin, Düsseldorf, München, Stuttgart
End of News DGAP News-Service
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