Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing
drugs to treat cancer by the targeted killing of cancer stem cells,
today announced the initiation of COMMAND (Control Of Mesothelioma
with MAiNtenance Defactinib). COMMAND is a
registration-directed trial of lead cancer stem cell inhibitor
defactinib (VS-6063) in patients with malignant pleural mesothelioma, a
highly aggressive form of lung cancer with a high percentage of cancer
stem cells.
COMMAND is a registration-directed, double-blind, placebo-controlled
trial with Progression Free Survival (PFS) and Overall Survival (OS) as
the primary endpoints. The study incorporates the opportunity to enrich
for patients with tumors low in the biomarker, merlin. Preclinical and
early clinical research has demonstrated that low merlin levels are
predictive of increased effectiveness of FAK inhibitors such as
defactinib. The COMMAND study will stratify patients to evaluate the
effect of defactinib in both the overall patient population and the
subgroup that are merlin low.
“FAK inhibition holds significant potential in malignant pleural
mesothelioma, a cancer whose aggressiveness and treatment resistance
proves all too often to be devastating for patients,” said Dr. Joanna
Horobin, Verastem Chief Medical Officer. “Development of a drug that
preferentially kills cancer stem cells is a promising approach, as many
standard-of-care treatments have been shown to either have no effect on,
or actually enrich the population of, these chemoresistant cells.”
COMMAND is expected to enroll approximately 350-400 patients at clinical
sites in 11 countries, including the US, UK, Australia, Canada, South
Africa, New Zealand and countries in mainland Europe. Eligible patients
who had a partial response or stable disease following standard
first-line therapy with platinum/pemetrexed will be stratified to merlin
low or high and then randomized 1:1 to receive either placebo or 400 mg
of defactinib twice daily.
“The incidence of mesothelioma, among the most aggressive and lethal
cancers, is increasing worldwide, underscoring an urgent need to expand
the very limited treatment options for patients fighting this disease,”
said Professor Dean Fennell, Chair of Thoracic Medical Oncology at the
University of Leicester, incoming President of the International
Mesothelioma Interest Group (iMig) and Coordinating Investigator for
COMMAND in the UK. “This well-designed study is expected to deliver a
one-two punch to the tumor by treating with defactinib following
first-line therapy that achieves initial disease control, but has not
eliminated the cancer stem cells nor historically stopped disease
progression, in an attempt to prolong clinical response. There is
significant enthusiasm within the mesothelioma community for the COMMAND
study.”
Verastem was recently granted orphan drug designation for defactinib in
mesothelioma by the U.S. Food and Drug Administration’s Office of Orphan
Drug Products. The Company received a similar designation from the
European Commission in June of this year. Adding to an intellectual
property portfolio including composition of matter for defactinib, these
designations provide eligibility for seven- and ten-year periods of
market exclusivity, respectively, after product approval, as well as
other development incentives.
“Timely initiation of this study marks yet another important milestone
in our development of defactinib, and highlights the diligent execution
of our clinical strategy by Verastem’s research and development team,”
said Robert Forrester, Verastem President and Chief Executive Officer.
“We will provide an update on the progress of this study in our year-end
update in the first quarter of 2014.”
In addition to defactinib in mesothelioma, Verastem recently announced
the completion of the Phase 1 stage and initial data from an ongoing
Phase 1/1b study of defactinib in combination with weekly paclitaxel for
patients with ovarian cancer. Verastem expects to initiate additional
studies of defactinib including a Phase 2 trial in KRAS-mutated
Non-Small Cell Lung Cancer and a Phase 1 study in Japan during the third
quarter of 2013. The Company also announced the recent initiation of a
Phase 1 study of FAK inhibitor VS-4718 in patients with advanced cancer,
and that it expects to enter the dual mTORC1/2 and PI3K inhibitor
VS-5584 into the clinic later this year.
About Malignant Pleural Mesothelioma
Malignant pleural mesothelioma is an aggressive form of cancer that
occurs in the mesothelium, the thin layer of tissue that covers the
lungs. Mesothelioma is associated with exposure to asbestos in most
cases. According to the World Health Organization, a total of 59,000
deaths occur worldwide each year due to mesothelioma. Most mesotheliomas
begin as one or more nodules that progressively grow to form a solid
coating of tumor surrounding the lung leading to eventual suffocation
and death. A high percentage of mesotheliomas contain cancer stem cells
which are generally resistant to the currently available treatment
options for advanced mesothelioma.
About Defactinib
Defactinib (VS-6063) is an oral compound designed to target cancer stem
cells through the potent inhibition of focal adhesion kinase (FAK).
Cancer stem cells are an underlying cause of tumor resistance to
chemotherapy, recurrence and ultimate disease progression. Research by
Robert Weinberg, Ph.D., scientific cofounder and chair of Verastem’s
Scientific Advisory Board, and Verastem has demonstrated that the FAK
pathway is critical for the growth and survival of cancer stem cells.
Defactinib is currently being studied in a registration-directed COMMAND
trial in mesothelioma and a Phase 1/1b study in ovarian cancer. A Phase
2 trial in KRAS-mutated Non-Small Cell Lung Cancer and a Phase 1 study
in Japan are expected to begin in the third quarter of 2013. Defactinib
has been granted orphan drug designation in the U.S. and E.U. for use in
mesothelioma.
About Verastem, Inc.
Verastem, Inc. (NASDAQ:VSTM) is discovering and developing drugs to
treat cancer by the targeted killing of cancer
stem cells. Cancer stem cells are an underlying cause of tumor
recurrence and metastasis. Verastem is developing small molecule
inhibitors of signaling pathways that are critical to cancer stem cell
survival and proliferation: FAK, PI3K/mTOR and Wnt. For more
information, please visit www.verastem.com.
Forward-looking statements:
This press release includes forward-looking statements about the
Company’s strategy, future plans and prospects, including statements
regarding the development of the Company’s compounds, including VS-6063,
VS-4718 and VS-5584, and the Company’s FAK, PI3K/mTOR and diagnostic
programs generally, the timeline for clinical development and regulatory
approval of the Company’s compounds, the expected timing for the
reporting of data from ongoing trials, the structure of the Company’s
planned or pending clinical trials and estimates of the Company’s
ability to fund operations. The words “anticipate,” “appear,” “believe,”
“estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,”
“target,” “potential,” “will,” “would,” “could,” “should,” “continue,”
and similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain these
identifying words. Each forward-looking statement is subject to risks
and uncertainties that could cause actual results to differ materially
from those expressed or implied in such statement. Applicable risks and
uncertainties include the risks that the preclinical testing of the
Company’s compounds and preliminary data from clinical trials may not be
predictive of the results or success of later clinical trials, that data
may not be available when we expect it to be that the Company will be
unable to successfully complete the clinical development of its
compounds, including VS-6063, VS-4718 and VS-5584, that the development
of the Company’s compounds will take longer or cost more than planned,
and that the Company’s compounds will not receive regulatory approval or
become commercially successful products. Other risks and uncertainties
include those identified under the heading “Risk Factors” in the
Company’s Annual Report on Form 10-K for the year ended December 31,
2012 and in any subsequent SEC filings. The forward-looking statements
contained in this presentation reflect the Company’s current views with
respect to future events, and the Company does not undertake and
specifically disclaims any obligation to update any forward-looking
statements.
Copyright Business Wire 2013