4SC Announces First Patient Dosed in Phase I/II SHORE Study in KRAS-Mutant Colorectal Cancer Patients with Resminostat
January 20 2011 - 1:55AM
Business Wire
4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and
development company, today announced that the first patient has
been dosed in the Phase I/II SHORE study with the oral pan-histone
deacetylase (HDAC) inhibitor resminostat as a second-line treatment
for patients with advanced and metastatic colorectal KRAS-mutant
cancer.
SHORE is a randomised, open-label, multi-centre, two-arm Phase
I/II study in 70 patients that will evaluate the efficacy, safety
and pharmacokinetics of resminostat, in combination with FOLFIRI, a
chemotherapy regimen for the treatment of colorectal cancer, versus
FOLFIRI alone in the control arm. In the combination arm of the
study patients will be treated with the maximum tolerated dose of
resminostat in combination with FOLFIRI, which will be determined
through an initial dose-escalation phase, evaluating 200mg, 400mg,
600mg and 800mg of reminostat together with FOLFIRI in
approximately 20 patients. An optional extension to this dosing
scheme has been included to also evaluate 300mg, 500mg and 700mg of
reminostat once daily, as well as 300mg and 400mg resminostat twice
daily, each dose in combination with FOLFIRI. In the combination
arm resminostat will be given orally over five consecutive days
(d1-5), followed by a nine day (d6-14) treatment free period
resulting in treatment cycles of 14 days (5+9 scheme) each. FOLFIRI
will be given on day three and four (d3 and d4) of each of these 14
day treatment cycles. In both study arms, treatment may continue
until there is evidence of progressive disease or the patient
leaves the trial for other reasons. The study will be performed at
approximately ten centres in Germany.
The primary endpoint of the study is to determine the
progression free survival (PFS). The secondary endpoints include
progression free survival rate (PFSR) after eight weeks and every
eight weeks thereafter, the analysis of time-to-progression (TTP),
overall survival (OS), analysis of drug safety, tolerability,
pharmacokinetics and the investigation of biomarkers.
In recent years it has been discovered that colorectal cancer
patients with KRAS mutant tumours do not respond to treatment with
EGFR inhibitors. This has changed treatment practices, resulting in
treatment with EGFR inhibitors targeting only patients with KRAS
wild type tumours. As a result, a new treatment need has arisen for
patients that carry mutated KRAS genes, which account for
approximately 40% of metastatic colorectal cancer patients.
HDAC enzymes have emerged as promising targets in colorectal
cancer over the last decade, since they have proven to be important
for colon cancer cell survival. Based on both in vitro and in vivo
testing it has been shown that especially the frequently observed
high expression of HDAC-2 in colon cancer cells is associated with
their enhanced survival capability. Resminostat, as a pan-HDAC
inhibitor, reduces the activity of a variety of HDAC enzymes,
including HDAC-2. Consequently, resminostat yielded promising
results in preclinical models of colorectal cancer, as it also
sensitized colorectal cancer cells to standard
chemotherapeutics.
'By evaluating the efficacy of resminostat in patients carrying
KRAS-mutant tumours, we hope to open a second-line treatment option
for this colorectal cancer patient population where there is an
increased unmet medical need since they cannot be treated with
current EGFR targeting agents,' stated Bernd Hentsch, Chief
Development Officer. 'With the commencement of the SHORE study we
have delivered on our clinical development strategy for
resminostat, which is assessing its efficacy in mono- and
combination therapy in hematological and solid tumours. We are very
excited about 2011, as we expect Phase II results for both the
hepatocellular cancer SHELTER study and the Hodgkin's lymphoma
SAPHIRE study.'
More information about this trial can be found on
www.clinicaltrials.gov.
About Resminostat (4SC-201)
Resminostat (4SC-201) is an oral pan-histone-deacetylase (HDAC)
inhibitor. HDAC inhibitors 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. Resminostat is currently in Phase II
studies as a second line treatment for advanced hepatocellular
carcinoma and colorectal cancer in KRAS-mutant patients as well as
a third-line treatment in Hodgkin's lymphoma. In a completed Phase
I trial in patients with various different cancer types, stable
disease was achieved in over 50% of the patients, whilst the
treatment was well tolerated and showed a positive, differentiating
pharmacological profile to other drugs in this class.
About Colorectal Cancer Colorectal cancer is the second leading
cause of death from cancers in the western world. It incorporates
colon cancer, which is based in the large intestine (colon), the
lower part of your digestive system. It also includes rectal
cancer, which affects the last inches of the colon. Colon cancer is
2.5 times more common than rectal cancer, while rectal cancers
account for fewer than 4% of all lower gastrointestinal
cancers.
Current treatment of advanced colorectal cancer is based on
chemotherapy regimens, such as FOLFIRI and FOLFOX, in combination
with targeted antibodies, frequently as a first line treatment.
These antibodies inhibit various growth factors or receptors that
are involved in the progress of the cancer disease. Currently these
approaches focus on targeting vascular endothelial growth factor
(VEGF), an angiogenic signaling protein or epidermal growth factor
receptors (EGFR).
About 4SC
4SC AG (ISIN DE0005753818) is a drug discovery and development
company focused on autoimmune and cancer indications. Vidofludimus
(4SC-101), a small molecule, is currently in Phase II development
in rheumatoid arthritis and inflammatory bowel disease (IBD), for
which positive results from a Phase IIa study were recently
reported. The company's lead oncology compound, resminostat
(4SC-201), a pan-histone deacetylase (HDAC) inhibitor, is in Phase
II trials in hepatocellular carcinoma, Hodgkin's lymphoma and
KRAS-mutant colorectal cancer. Two further oncology compounds,
4SC-203 and 4SC-205, are in Phase I studies. 4SC develops drug
candidates until proof-of-concept in order to generate value
creating partnerships with the pharmaceutical industry in return
for advance and milestone payments as well as royalties.
Founded in 1997, 4SC has 94 employees and has been listed on the
Prime Standard of the Frankfurt Stock Exchange since December
2005.
For further information, please visit www.4sc.com.
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.
Language: English Company: 4SC AG Am Klopferspitz 19a 82152
Martinsried Deutschland Phone: +49 (0)89 7007 63-0 Fax: +49 (0)89
7007 63-29 E-mail:
public@4sc.com
Internet:
www.4sc.de
ISIN: DE0005753818 WKN: 575381 Listed: Regulierter Markt in
Frankfurt (Prime Standard); Freiverkehr in Berlin, Düsseldorf,
München, Stuttgart
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