Syndax Pharmaceuticals' Entinostat Shows Clinical Promise in Patients with Advanced Hormone Refractory Breast Cancer
- Data to be Presented at the American Society of Clinical Oncology Annual Meeting -
WALTHAM, Mass., June 4 /PRNewswire/ -- Syndax Pharmaceuticals,
Inc., a clinical-stage epigenetics oncology company, reported final
results from the Phase 2, open-label ENCORE 303 trial in
post-menopausal women with advanced, estrogen receptor (ER)
positive breast cancer who were progressing on aromatase inhibitor
(AI) therapy. Safety and efficacy results from the trial will be
presented in a poster at the American Society of Clinical Oncology
(ASCO) annual meeting in Chicago, IL tomorrow, Saturday, June 5,
"These findings are significant given that the patients enrolled
were heavily hormonally pre-treated and relatively hormone
resistant," said Joanna Horobin, president and chief executive
officer of Syndax. "Resistance to AI therapy is multi-factorial and
involves up-regulation of growth factor signaling pathways and
down-regulation of estrogen receptor expression which may result
from epigenetic modifications to the DNA and associated proteins.
The disease stabilization achieved with the addition of entinostat
supports our hypothesis that entinostat has the ability to
normalize gene expression, thereby restoring sensitivity to
targeted agents. We are optimistic that our ongoing ENCORE 301
study, a double-blind, randomized, placebo-controlled phase 2 study
of entinostat in combination with the aromatase inhibitor
exemestane, will provide further evidence supporting the clinical
benefit and tolerability of entinostat in combination with
The primary endpoint of the study was Clinical Benefit Rate
(CBR), defined as the proportion of patients who experience a
complete or partial response or stable disease (SD) during the
first six cycles of study treatment. Of the 26 evaluable patients
in the ENCORE 303 study, one achieved a partial response (PR) and
three achieved SD of greater than six months. The CBR of 15.4%
exceeded the pre-specified rate of 5% defined in the study design
with a p-value of 0.039. An additional six patients experienced SD
between four and six months.
Secondary endpoints were objective response (OR) and
progression-free survival (PFS), which were 3.9% and a median of
4.8 months, respectively. Overall survival, pharmacokinetics and
correlation of selected biomarkers with clinical outcome were also
measured. The most common adverse events considered to be related
to entinostat were fatigue, nausea and diarrhea. No unexpected side
effects were observed.
Syndax is also presenting two posters during the Society's new
"Trials in Progress" session. These include abstract TPS128, which
reviews ENCORE 301, a double-blind, randomized, placebo-controlled
phase 2 study of entinostat in combination with exemestane, an
aromatase inhibitor, in 114 post-menopausal women with ER positive
metastatic breast cancer; and abstract TPS298, which reviews ENGAGE
501, an open-label, multicenter Phase 2 study in patients with
Hodgkin's lymphoma. Data are anticipated from ENCORE 301 and ENGAGE
501 within 12 months.
Information regarding the ASCO presentations and full abstracts
may be found on the ASCO website at http://abstract.asco.org/index20100505.html.
Entinostat is an orally bioavailable, highly selective, class I
histone deacetylase (HDAC) inhibitor with a long half-life that may
allow for weekly or every-other-week dosing. Entinostat is
currently being investigated in several randomized, phase 2
clinical studies including advanced ER+ breast cancer in
combination with aromatase inhibitors and separately in combination
with exemestane and Hodgkin's lymphoma as a single agent.
Entinostat is also being studied in advanced non-small-cell lung
cancer and in advanced colorectal cancer in combination with
azacitidine under a Cooperative Research and Development Agreement
(CRADA) with the NIH.
Research has shown that HDACs are involved in the expression of
various genes, such as the estrogen receptor, that regulate cell
growth, differentiation and apoptosis. Such genes are frequently
silenced in cancer cells through the over-expression of enzymes
including HDACs. HDACs are therefore recognized as promising
targets for cancer treatment. Further, studies have demonstrated
that HDAC inhibition can significantly enhance anti-cancer activity
when used in combination with a broad range of anti-cancer agents.
The potential therefore exists to overcome tumor resistance to
Syndax Pharmaceuticals, Inc. is a Waltham, MA-based,
oncology-focused pharmaceutical company. Syndax is building a
portfolio of new oncology products to extend and improve the lives
of patients by developing and commercializing novel cancer
therapies in optimized, mechanistically driven combination
regimens. Formed in 2005, the company's intellectual property is
based on work from scientific founder Ronald Evans, PhD, recipient
of the 2004 Albert Lasker Prize for Basic Medical Research, a
Member of the National Academy of Sciences, a professor at the Salk
Institute for Biological Studies and a Howard Hughes Medical
Syndax holds rights to entinostat from Bayer Schering Pharma and
is backed by top-tier Venture Capital firms: Domain Associates, MPM
Capital, Avalon, Pappas and Forward Ventures.
Source: Syndax Pharmaceuticals, Inc.
CONTACT: Kathryn Penkus Corzo, RPh of Syndax Pharmaceuticals,
+1-781-577-2822, email@example.com; or Aline Schimmel of WCG, +1-312-646-6295,
firstname.lastname@example.org, for Syndax Pharmaceuticals, Inc.
Web Site: http://www.syndax.com/
Posted: June 2010