Preliminary Data on VS-6766 and Defactinib
Combination Continues to Show Encouraging Response Rates,
Durability and a Favorable Safety Profile in KRAS Mutant Low-Grade
Serous Ovarian Cancer in Investigator-Initiated Trial
New Preclinical Data Demonstrating Synergy and
Tumor Regression with G12C Inhibitors in Combination with VS-6766
and FAK Inhibitor In Vitro and In Vivo Also Presented
Management to Host Investor Conference Call
Today at 8:00 AM ET
Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology),
a biopharmaceutical company committed to advancing new medicines
for patients battling cancer, today announced updated results from
the ongoing investigator-initiated Phase 1/2 FRAME study evaluating
VS-6766, its RAF/MEK inhibitor, in combination with defactinib, its
FAK inhibitor, which demonstrated robust response rates, duration
of response and a favorable safety profile in patients with
low-grade serous ovarian cancer (LGSOC). These data will be
presented in a virtual oral presentation today by Dr. Udai Banerji
from The Institute of Cancer Research and The Royal Marsden at the
2nd Annual RAS-Targeted Drug Development Summit.
“Existing treatments for patients with LGSOC are limited by
either 10-25% response rates and/or increased toxicities, leading
to high discontinuation rates. The FRAME data being presented today
continue to demonstrate that RAF/MEK inhibition combined with FAK
inhibition is well tolerated with a 56% overall response rate (ORR)
in patients with KRAS-G12 mutant LGSOC and a 41% ORR in the overall
LGSOC population. These data are still actively maturing with more
than half of the patients still on treatment as of the data cutoff
date, and responses in this patient population tend to deepen over
time,” said Dan Paterson, President and Chief Operating Officer of
Verastem Oncology. “The response rates from this expanded data set
are highly encouraging, consistent with the prior positive data
from this study, and continue to speak to the significant potential
of the VS-6766/defactinib combination for patients battling
LGSOC.”
Verastem recently met with the Food and Drug Administration
(FDA), and the FDA is supportive of the Company’s adaptive study
design for the planned Phase 2 registration-directed trials
evaluating VS-6766 and defactinib in patients with recurrent LGSOC.
Verastem expects to commence registration-directed clinical trials
in both recurrent LGSOC and KRAS mutant non-small cell lung cancer
by the end of 2020. Assuming a positive outcome from these
registration-directed trials, Verastem expects to submit New Drug
Applications to the FDA requesting accelerated approval for the
VS-6766/defactinib combination in both LGSOC and KRAS mutant
NSCLC.
Updated Phase 1/2 FRAME Study Results in Patients with
LGSOC
Among the patients with LGSOC (n=17), the overall response rate
(ORR) was 41% (7 of 17 patients), all partial responses (PRs).
Among the patients with KRAS-G12 mutant LGSOC (n=9), the ORR was
56% (5 of 9 patients). Of the seven patients who responded, five
had received one or more prior MEK inhibitors. In patients with
KRAS mutant LGSOC receiving the recommended Phase 2 dosing (RP2D)
regimen, the ORR was 50% (3 of 6 patients). The LGSOC cohort of the
FRAME study remains ongoing, with 53% (9 of 17 patients) still on
study as of the data cutoff date of August 17, 2020, with three
patients on treatment for two years or more.
The most common Grade ≥3 treatment-related adverse events
(TEAEs) observed for the recommended Phase 2 dosing regimen were
rash (4%) and elevated creatine kinase (4%). No patients
discontinued from the FRAME study due to TEAEs.
The novel, intermittent, combination dosing schedule used in the
FRAME study continues to show encouraging clinical activity in
patients with KRAS mutant LGSOC, including in patients who had
previously progressed following treatment with a MEK inhibitor.
“These updated safety and efficacy results in both KRAS mutant
LGSOC as well as the overall LGSOC population are highly
encouraging. Of particular note in this early look at the data, is
the strong, 50% response rate, durability, and tumor reduction seen
in patients with KRAS mutant LGSOC receiving the recommended Phase
2 dosing (RP2D) regimen, which is the regimen we will be taking
into our upcoming registration-directed study,” said Brian Stuglik,
Chief Executive Officer of Verastem Oncology. “With nine out of 11
patients at RP2D active in the study and responses still
developing, we look forward to continued data outputs from this
study and we remain on track to commence Phase 2
registration-directed trials in both LGSOC and KRAS mutant NSCLC by
the end of this year.”
Preclinical Results from Studies Investigating VS-6766 and
Defactinib in Combination with G12C Inhibitors
KRAS-G12C inhibitors may benefit from novel combination
approaches to enhance their inhibition of the ERK signaling
pathway. In the preclinical results that will be presented today at
the meeting, VS-6766 showed synergy with KRAS-G12C inhibitors in
reducing cancer cell viability across a panel of KRAS-G12C mutant
NSCLC and colorectal cancer (CRC) cell lines. This enhanced
cellular anti-cancer activity of the combination correlated with
deeper and more durable inhibition of ERK pathway signaling
relative to G12C inhibition alone. In KRAS-G12C mutant NSCLC models
in mice, the RAF/MEK dual inhibitor VS-6766 was more effective than
trametinib when compared at equal dose level both alone and in
combination with a G12C inhibitor. In the KRAS-G12C NSCLC models
tested, the combination of G12C inhibitor with VS-6766 and FAK
inhibitor induced tumor regressions of ≥30% in all mice.
“The anti-tumor effects of VS-6766 were generally comparable to
those of KRAS-G12C inhibitors in KRAS-G12C NSCLC models in mice and
were stronger than the effects of trametinib at a comparable dose,”
said Jonathan Pachter, Ph.D., Chief Scientific Officer of Verastem
Oncology. “The tumor regressions observed with the triple
combination of VS-6766, FAK inhibitor and G12C inhibitor were
particularly striking. These data support clinical evaluation of
VS-6766 and defactinib with G12C inhibitors in patients with
KRAS-G12C mutant tumors.”
About the Phase 1/2 FRAME Study
The FRAME study is an open-label, investigator-initiated study
that is designed to assess safety, dose response and preliminary
efficacy of the VS-6766/defactinib combination in patients with
KRAS mutant solid tumors, including LGSOC, non-small cell lung
cancer (NSCLC) and colorectal cancer (CRC). The FRAME study is
being led by Dr. Banerji and is being conducted in the United
Kingdom. In this study, VS-6766 was administered using a
twice-weekly dose escalation schedule and was administered three
out of every four weeks. Defactinib was administered using a
twice-daily dose escalation schedule, also three out of every four
weeks. Dose levels were assessed in three cohorts: cohort 1
(VS-6766 3.2mg, defactinib 200mg); cohort 2a (VS-6766 4mg,
defactinib 200mg); and cohort 2b (VS-6766 3.2mg, defactinib 400mg).
The recommended Phase 2 dose was determined to be VS-6766 3.2mg,
defactinib 200mg. The FRAME study is now expanding to include new
cohorts in pancreatic cancer, KRAS mutant endometrial cancer and
KRAS-G12V mutant NSCLC.
Details for the RAS-Targeted Drug Development Summit oral
presentation are as follows:
Title: Clinical Combinations: Dual RAF-MEK Inhibitor
& FAK for Treatment of KRAS Mutant Cancers With a Focus on Low
Grade Ovarian Cancer Lead author: Udai Banerji, The
Institute of Cancer Research and The Royal Marsden Date and
Time: Wednesday, September 16, 2020; 3:35 p.m. ET (12:35 p.m.
PT)
Title: Synergistic Combinations with the Dual RAF/MEK
Inhibitor VS-6766 to Overcome Resistance Mechanisms Lead
author: Jonathan Pachter, Verastem Oncology Date and
Time: Wednesday, September 16, 2020; 12:10 p.m. ET (9:10 a.m.
PT)
Conference Call and Webcast Information
The Verastem Oncology management team will host a conference
call and webcast on Wednesday, September 16, 2020, at 8:00 AM ET to
discuss the updated Phase 1/2 FRAME study data. The call can be
accessed by dialing (877) 341-5660 (US and Canada) or (315)
625-3226 (international), five minutes prior to the start of the
call and providing the passcode 5278200.
The live, listen-only webcast of the conference call can be
accessed by visiting the investors section of the Company's website
at www.verastem.com. A replay of the webcast will be archived on
the Company's website for 90 days following the call.
About VS-6766
VS-6766 (formerly known as CH5126766, CKI27 and RO5126766) is a
unique inhibitor of the RAF/MEK signaling pathway. In contrast to
other MEK inhibitors in development, VS-6766 blocks both MEK kinase
activity and the ability of RAF to phosphorylate MEK. This unique
mechanism allows VS-6766 to block MEK signaling without the
compensatory activation of MEK that appears to limit the efficacy
of other inhibitors.
About Defactinib
Defactinib (VS-6063) is an oral small molecule inhibitor of FAK
and PYK2 that is currently being evaluated as a potential
combination therapy for various solid tumors. The Company has
received Orphan Drug designation for defactinib in ovarian cancer
and mesothelioma in the US, EU and Australia. Preclinical research
by Verastem Oncology scientists and collaborators at world-renowned
research institutions has described the effect of FAK inhibition to
enhance immune response by decreasing immuno-suppressive cells,
increasing cytotoxic T cells, and reducing stromal density, which
allows tumor-killing immune cells to enter the tumor.1,2
About the VS-6766/Defactinib Combination
RAS mutant tumors are present in ~30% of all human cancers, have
historically presented a difficult treatment challenge and are
often associated with significantly worse prognosis. Challenges
associated with identifying new treatment options for these types
of cancers include resistance to single agents, identifying
tolerable combination regimens with MEK inhibitors and new RAS
inhibitors in development addressing only a minority of all RAS
mutated cancers.
The combination of VS-6766 and defactinib has been found to be
clinically active in patients with KRAS mt tumors. In an ongoing
investigator-initiated Phase 1/2 FRAME study, the combination of
VS-6766 and defactinib is being evaluated in patients with LGSOC,
KRASmt NSCLC and colorectal cancer (CRC). Updated data from this
study presented at the 2nd Annual RAS-Targeted Drug Development
Summit in September 2020 demonstrated a 56% overall response rate
and long duration of therapy among patients with KRAS-G12 mt LGSOC.
Based on an observation of higher response rates seen in NSCLC
patients with KRAS-G12V mutations in the study, Verastem will also
be further exploring the role of VS-6766 and defactinib in
KRAS-G12V NSCLC. The FRAME study was expanded in August 2020 to
include new cohorts in pancreatic cancer, KRASmt endometrial cancer
and KRAS-G12V NSCLC.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a development-stage
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on novel small
molecule drugs that inhibit critical signaling pathways in cancer
that promote cancer cell survival and tumor growth, including
RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For
more information, please visit www.verastem.com.
Forward-Looking Statements Notice
This press release includes forward-looking statements about
Verastem Oncology’s strategy, future plans and prospects, including
statements related to the potential clinical value of the
RAF/MEK/FAK combination and the timing of commencing a
registration-directed trial for the RAF/MEK/FAK combination. The
words "anticipate," "believe," "estimate," "expect," "intend,"
"may," "plan," "predict," "project," "target," "potential," "will,"
"would," "could," "should," "continue," “can,” “promising” 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 and
uncertainties, among other things, regarding: the success in the
development and potential commercialization of our product
candidates, including defactinib in combination with VS-6766; the
occurrence of adverse safety events and/or unexpected concerns that
may arise from additional data or analysis or result in
unmanageable safety profiles as compared to their levels of
efficacy; our ability to obtain, maintain and enforce patent and
other intellectual property protection for our product candidates;
the scope, timing, and outcome of any legal proceedings; decisions
by regulatory authorities regarding labeling and other matters that
could affect the availability or commercial potential of our
product candidates; whether preclinical testing of our product
candidates and preliminary or interim data from clinical trials
will be predictive of the results or success of ongoing or later
clinical trials; that the timing, scope and rate of reimbursement
for our product candidates is uncertain; that third-party payors
(including government agencies) may not reimburse; that there may
be competitive developments affecting our product candidates; that
data may not be available when expected; that enrollment of
clinical trials may take longer than expected; that our product
candidates will experience manufacturing or supply interruptions or
failures; that we will be unable to successfully initiate or
complete the clinical development and eventual commercialization of
our product candidates; that the development and commercialization
of our product candidates will take longer or cost more than
planned; that we or Chugai Pharmaceutical Co., Ltd. will fail to
fully perform under the VS-6766 license agreement; that we may not
have sufficient cash to fund our contemplated operations; that we
may be unable to make additional draws under our debt facility or
obtain adequate financing in the future through product licensing,
co-promotional arrangements, public or private equity, debt
financing or otherwise; that we will be unable to execute on our
partnering strategies for defactinib in combination with VS-6766;
that we will not pursue or submit regulatory filings for our
product candidates; and that our product candidates will not
receive regulatory approval, become commercially successful
products, or result in new treatment options being offered to
patients.
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, 2019 as filed with the Securities
and Exchange Commission (SEC) on March 11, 2020 and in any
subsequent filings with the SEC. The forward-looking statements
contained in this press release reflect Verastem Oncology’s views
as of the date hereof, and the Company does not assume and
specifically disclaims any obligation to update any forward-looking
statements whether as a result of new information, future events or
otherwise, except as required by law.
References
1 Chénard-Poirier, M. et al. Results from the biomarker-driven
basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor,
in RAS- or RAF-mutated malignancies including multiple myeloma.
Journal of Clinical Oncology 2017: 35.
10.1200/JCO.2017.35.15_suppl.2506.
2 https://clinicaltrials.gov, NCT03875820
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version on businesswire.com: https://www.businesswire.com/news/home/20200916005214/en/
Investors: John Doyle Vice President, Investor Relations &
Finance +1 781-469-1546 jdoyle@verastem.com
Media: Lisa Buffington Corporate Communications +1 781-292-4205
lbuffington@verastem.com
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