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Verastem Presents Data at the 2014 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
Results from the Phase 1 Dose Escalation Study of VS-6063 in Japanese
Patients and
“We are pleased that the safety and pharmacokinetic profile observed in
our Phase 1 study of VS-6063 in Japanese patients was consistent with
that seen in the US Phase 1 study, permitting the inclusion of Japanese
sites in COMMAND, the registration-directed study of VS-6063 in patients
with mesothelioma following frontline chemotherapy. Also, we noted that
the one patient in the Phase 1 study with relapsed mesothelioma appeared
to receive clinical benefit with disease stabilization of almost 6
months,” said Dr.
“The preclinical posters presented at EORTC this year continue to expand
our understanding of the activity of VS-6063 and VS-5584 along with
their underlying biological mechanisms,” said Dr.
A summary of the data presented by
Title: A first-in-Asian phase I dose escalation study to
evaluate the safety and pharmacokinetics of VS-6063 (defactinib), a
focal adhesion kinase inhibitor in subjects with non-hematologic
malignancies
Abstract #: 296
Poster Board #: 076
Date:
Time:
Location:
Exhibition Hall
Summary: Results were presented from a
first-in-
The Japanese Phase 1 is an open-label, dose-escalation study that enrolled nine subjects who received single-agent VS-6063 (200, 400 or 600mg; n=3 in each dose cohort) BID. The study results demonstrated that VS-6063 was well tolerated at all dose levels. There were no serious adverse events or evidence of dose-limiting toxicity. Pharmacokinetic results from the recommended Phase 2 dose of 400mg BID were consistent with previously reported data in non-Japanese subjects. These safety and pharmacokinetic results supported the entry of Japanese subjects at the RP2D into the ongoing multinational trial (COMMAND) of VS-6063 in malignant pleural mesothelioma (MPM) patients.
A copy of the poster presentation is available at http://bit.ly/R3M6wc.
Title: FAK inhibitor VS-6063 (defactinib) targets
mesothelioma cancer stem cells which are enriched by standard of care
chemotherapy
Abstract #: 302
Poster Board #: 082
Date:
Time:
Location:
Exhibition Hall
Summary: MPM is an aggressive tumor in the
lining of the lung often resulting from prior exposure to asbestos.
Median overall survival with standard of care chemotherapy is only 12
months from diagnosis. This poor prognosis may be attributable at least
in part to CSCs which are resistant to chemotherapy and can mediate
cancer recurrence and progression. FAK has been shown to play an
essential role in the survival, self-renewal and tumor-initiating
capability of CSCs.
In the preclinical models and patient biopsies studied, two standard-of-care agents, pemetrexed and platinum, enrich the proportion of CSCs. In direct contrast, FAK inhibitor, VS-6063, markedly reduced the proportion of CSCs in vitro, in vivo and in tumors of VS-6063-treated mesothelioma patients. VS-6063 treatment also delayed tumor regrowth following cisplatin plus pemetrexed treatment in vivo. These data provide the rationale for the current clinical testing of VS-6063 in Verastem’s registration-directed COMMAND trial, evaluating VS-6063 following treatment with pemetrexed plus platinum to potentially prolong response to front line chemotherapy in patients with mesothelioma.
A copy of the poster presentation is available at http://bit.ly/R3M6wc.
Title: PI3K/mTOR inhibitor VS-5584 targets cancer stem cells and
prevents tumor regrowth after chemotherapy in preclinical models of
small cell lung cancer
Abstract #: 439
Poster Board
#: 011
Date:
Time:
Location: Exhibition Hall
Summary: Small
cell lung cancer (SCLC) is a highly aggressive malignancy with a 5‐year
overall survival rate of only 5‐10%. Most patients with SCLC initially
respond to chemotherapy but subsequently experience aggressive tumor
recurrence, which may be attributed to the presence of CSCs.
The study results presented here demonstrated that VS‐5584 inhibits proliferation and induces apoptosis in SCLC cell lines in vitro and exhibited antitumor activity in SCLC xenograft models in vivo. In addition, VS‐5584 also exhibited synergistic activity with standard‐of‐care agents, cisplatin and etoposide, in SCLC models. VS‐5584 is currently being evaluated in a Phase 1 clinical trial in patients with solid tumors, and the preferential targeting of CSCs by VS‐5584 in these preclinical models of SCLC provides the rationale for clinical development of VS‐5584 either as a single agent or in combination with chemotherapeutic agents to potentially extend time to relapse and improve outcome for patients with small cell lung cancer.
A copy of the poster presentation is available at http://bit.ly/R3M6wc.
Title: The cancer stem cell inhibitors VS-6063
(defactinib) and VS-5584 exhibit synergistic anticancer activity in
preclinical models of mesothelioma
Abstract #: 446
Poster
Board #: 018
Date:
Time:
Location: Exhibition Hall
Summary:
MPM is an aggressive cancer of the lining of the lung in which CSCs may
drive resistance to current chemotherapy. There is only one treatment
regimen approved for use, pemetrexed plus a platinum agent, which is
used as front‐line therapy and results in median overall survival of
only 12 months. Unfortunately, there are no approved second line options
for patients with actively progressing disease after front‐line therapy
where the median progression free survival reported in controlled
clinical trials is just six weeks.
In an effort to expand the mesothelioma patient population that may
potentially benefit from drugs targeting CSCs,
The study results demonstrated synergistic activity of VS‐6063 and VS‐5584 in mesothelioma models in vitro and in vivo. VS‐6063 and VS‐5584, alone and in combination, reduced the proportion of mesothelioma CSCs. In addition, single agent treatment with VS‐6063 or VS‐5584 reduced the viability of mesothelioma cells cultured in 3D matrigel, and the combination of VS‐6063 and VS‐5584 displayed synergistic reduction in cell viability based on multiple combination analysis models. When tested in vivo for reduction of mesothelioma tumor growth, VS‐6063 and VS‐5584 were each active as single agents. In combination, VS‐5584 further enhanced the antitumor efficacy of VS‐6063 in this model. The combination of VS‐6063 and VS‐5584 represents a novel therapeutic approach and these data support the clinical evaluation of the combination of VS‐6063 and VS‐5584 in patients with relapsed mesothelioma following front‐line therapy.
A copy of the poster presentation is available at http://bit.ly/R3M6wc.
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
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.
About COMMAND
COMMAND is a registration-directed, double-blind, placebo-controlled trial of VS-6063 in patients with malignant pleural mesothelioma. The primary endpoints of COMMAND are progression free survival (PFS) and overall survival (OS). VS-6063 targets cancer stem cells which are an underlying cause of tumor progression and recurrence. The design of COMMAND allows the opportunity to enrich for patients with tumors low in the biomarker, merlin. Preclinical and early clinical research has demonstrated that low merlin levels may be predictive of increased effectiveness of FAK inhibitors such as VS-6063. The COMMAND study stratifies patients to evaluate the effect of VS-6063 in both the overall patient population and the subgroup of patients whose tumors are low in merlin.
COMMAND is expected to enroll approximately 350-400 patients at clinical
sites in 12 countries, including the US,
About
Forward-looking statements:
This press release includes forward-looking statements about the
Company’s strategy, future plans and prospects, including statements
regarding the development and activity of the Company’s product
candidates, including VS-6063, or defactinib, and VS-5584, and the
Company’s FAK and PI3K/mTOR programs generally, the timeline for
clinical development and regulatory approval of the Company’s compounds,
including the proposed commencement of the VS-6063/VS-5584 combination
study, 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 product candidates and preliminary or interim data from
clinical trials 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 the Company will be unable to successfully
complete the clinical development of its product candidates, including
VS-6063 and VS-5584, that the development of the Company’s product
candidates will take longer or cost more than planned, and that the
Company’s product candidates 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
Source:
Verastem, Inc.
Brian Sullivan, 781-292-4214
bsullivan@verastem.com