-Results from a Window of Opportunity study in surgically-eligible
patients demonstrate a reduction in pFAK, cancer stem cell markers and
tumor size following 12 days of treatment with VS-6063-
BOSTON -- (Business Wire)
Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing
drugs to treat cancer by the targeted killing of cancer stem cells,
announced the presentation of clinical and preclinical data in oral
presentation and discussion sessions at the 12th
International Mesothelioma Interest Group (iMig) Conference being held
October 22-24, 2014, at the Cape Town International Conference Centre in
Cape Town, South Africa.
Professor Raphael Bueno, M.D., Chief of Thoracic Surgery, Brigham and
Women’s Hospital (BWH), Boston and Principal Investigator of Verastem’s
ongoing Window of Opportunity study presented preliminary clinical
results in an oral presentation. The study is evaluating the biomarker
response to VS-6063 (defactinib), an oral small molecule that targets
cancer stem cells through the inhibition of focal adhesion kinase (FAK)
in patients with resectable pleural mesothelioma. Biopsies of the tumor
are taken before and after oral administration of VS-6063 (400mg BID)
for 12 days. The study also measures tumor size using CT/PET scans
before and after the 12-day administration of VS-6063. All study
patients were enrolled at the BWH clinical site.
An analysis of the preliminary data (n=10) showed that VS-6063 reduced
FAK activity (pFAK-Y397) by an average of 70% in the patients evaluated
to date, and reduced the presence of cancer stem cell markers in the
post-treatment biopsies in 5 out of the 7 patients with evaluable paired
biopsies. Measurement of tumor size by CT/PET using RECIST modified for
mesothelioma confirmed that there was no progression of disease while on
the 12 day treatment with single agent VS-6063 in any of the 10
patients. Moreover, in 2 patients, tumor shrinkage consistent with a
partial response (-30%, -49%) was noted. VS-6063 was well tolerated with
no apparent negative impact on surgical outcome.
“These initial biopsy data show signs of activity against biomarkers of
cancer stem cells as well as intriguing reductions in tumor size, after
short-term exposure to single agent VS-6063,” said Dr. Bueno. “To follow
up on these encouraging results, the protocol is being amended to
explore more extended dosing in 10-15 additional patients with
mesothelioma prior to surgery. The window of opportunity before elective
surgery provides a novel platform for the clinical evaluation of
promising new agents for the treatment of this devastating disease.”
“This study was designed to evaluate potential biomarkers of response to
VS-6063 treatment in patients with pleural mesothelioma,” said Dr.
Joanna Horobin, Verastem Chief Medical Officer. “We are encouraged by
the biomarker response, and intrigued by the tumor shrinkage observed
after 12 days of VS-6063 administration. As we expand our clinical
program with VS-6063 in mesothelioma into other patient settings, we are
encouraged by these interesting signs of clinical activity.”
In addition to the Window of Opportunity study, Verastem is conducting
the registration-directed COMMAND study as a maintenance treatment
immediately following successful front-line therapy with Alimta and
cisplatin in patients with malignant pleural mesothelioma. Verastem
anticipates starting a study of VS-6063 and VS-5584 in combination for
patients with relapsed or progressive malignant pleural mesothelioma in
early 2015.
Verastem also presented preclinical data at the conference demonstrating
the ability of VS-6063 and the combination of VS-6063 and VS-5584 to
target and kill cancer stem cells in models of mesothelioma. In
addition, Professor Robert Weinberg, Ph.D., Whitehead
Institute/Massachusetts Institute of Technology, Verastem co-founder and
Chair of the Scientific Advisory Board, gave a keynote address to open
the symposium entitled: “Cancer Stem Cells as Target Pathways.” These
presentations support the ongoing and planned clinical trials that
Verastem is conducting in patients with mesothelioma.
A summary of the data presented by Verastem at the conference is below:
Oral Presentations and Discussions
iMig Special Keynote Lecture: “Cancer Stem Cells as Target
Pathways”
Presenter: Robert Weinberg, Ph.D., Whitehead
Institute/Massachusetts Institute of Technology, Verastem scientific
cofounder and chair of the Scientific Advisory Board
Date
and time: Wednesday, October 22, 2014, 8:50 AM (local time)
Link
to presentation: http://bit.ly/12otlcV
Presentation Title: “FAK Inhibitor VS-6063 (defactinib) Targets
Mesothelioma Cancer Stem Cells which are Enriched by Standard of Care
Chemotherapy”
Presenter: Paul Baas, M.D., Ph.D., Department
of Thoracic Oncology, The Netherlands Cancer Institute
Date
and time: Thursday, October 23, 2014, 3:30 PM (local time)
Link
to presentation: http://bit.ly/12otlcV
Presentation Title: “Determination of Biomarker Response in a
Phase II Window of Opportunity Study of Defactinib (VS-6063), a Focal
Adhesion Kinase (FAK) Inhibitor, in Subjects with Resectable MPM”
Presenter:
Raphael Bueno, M.D., Chief, Division of Thoracic Surgery,
Brigham & Women’s Hospital
Date and time: Thursday,
October 23, 2014, 3:45 PM (local time)
Link to presentation: http://bit.ly/12otlcV
Presentation Title: “The Cancer Stem Cell Inhibitors VS-6063
(defactinib) and VS-5584 Exhibit Synergistic Anticancer Activity in
Preclinical Models of Mesothelioma”
Presenter: Mitchell
Keegan, Ph.D., Vice President, Development, Verastem
Date
and time: Friday, October 24, 2014, 10:30 AM (local time)
Link
to presentation: http://bit.ly/12otlcV
Poster Presentation
Presentation Title:“COMMAND: A Phase 2 Randomized,
Double-Blind, Placebo-Controlled, Multicenter Study of Defactinib as
Maintenance Therapy in Subjects with Malignant Pleural Mesothelioma
which has not Progressed on at Least 4 cycles of Pemetrexed/Platinum
Therapy”
Presenter: Mitchell Keegan, Ph.D., Vice
President, Development, Verastem
Date and time: Thursday,
October 23, 2014, 10:30AM (local time)
Link to poster: http://bit.ly/12otlcV
Several of the above-mentioned studies were selected to be featured in
the “Best of iMig” series, which highlighted the most relevant studies
from the conference. Video of the presentations can be found at http://bit.ly/12d3OU1
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, there are a total of
59,000 cases of mesothelioma worldwide each year. 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 mesothelioma.
About VS-6063
VS-6063 (defactinib) is an orally available 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 FAK
activity is critical for the growth and survival of cancer stem cells.
VS-6063 is currently being studied in the registration-directed COMMAND
trial in mesothelioma (www.COMMANDmeso.com),
a “Window of Opportunity” study in patients with mesothelioma prior to
surgery, a Phase 1/1b study in combination with paclitaxel in patients
with ovarian cancer, and a trial in patients with Kras-mutated non-small
cell lung cancer. VS-6063 has been granted orphan drug designation in
the U.S. and EU for use in mesothelioma.
About VS-5584
VS-5584 is an orally available compound that has demonstrated potent and
highly selective activity against class 1 PI3K enzymes and dual
inhibitory actions against mTORC1 and mTORC2. In preclinical studies,
VS-5584 has been shown to reduce the percentage of cancer stem cells and
induce tumor regression in chemotherapy-resistant models. Verastem is
currently conducting a Phase 1 dose escalation trial of VS-5584 in
patients with advanced solid tumors and lymphomas.
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,
or defactinib, andVS-5584 and the Company’s FAK inhibition program and
PI3K/mTOR program 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, and the structure of the
Company’s planned or pending clinical trials. 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 or
interim data from clinical trials, including the Window of Opportunity
study, may not be predictive of the results or success of ongoing or
later clinical trials, that data may not be available when we expect it
to be, that enrollment of clinical trials may take longer than expected,
that the Company will be unable to successfully complete the clinical
development of its compounds, including VS-6063 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, 2013 and in any subsequent SEC filings. The forward-looking
statements contained in this press release 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.
Contacts:
Verastem, Inc.
Brian Sullivan, 781-292-4214
bsullivan@verastem.com
Source: Verastem, Inc.
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