No dose-limiting toxicities were observed in
the RAMP 203 first triplet combination cohort of avutometinib and
LUMAKRAS™ (sotorasib) plus defactinib in patients previously
treated with a G12C inhibitor
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced preliminary clinical data for the triplet
combination of avutometinib and sotorasib plus defactinib in the
RAMP 203 Phase 1/2 study in KRAS G12C mutant advanced non-small
cell lung cancer (NSCLC). No dose-limiting toxicities (DLTs) have
been observed in the triplet combination. RAMP 203 continues to
progress, with additional enrollment expected and an interim update
is planned to be presented at a medical meeting in the second half
of 2025.
“We continue to make progress across our pipeline to develop
novel therapies alone or in synergistic combinations that have the
potential to improve outcomes in RAS/MAPK pathway-driven cancers.
Defactinib, our oral FAK inhibitor, has been an important addition
to multiple clinical trials with avutometinib to address key
resistance mechanisms in parallel pathway signaling,” said Dan
Paterson, chief executive officer at Verastem Oncology. “Recently,
we added defactinib to the combination of avutometinib and
sotorasib in our RAMP 203 trial. Preliminary data for the triplet
combination have shown a generally favorable tolerability profile
and encouraging initial anti-tumor activity. We look forward to
progressing enrollment and evaluating the safety and efficacy of
the triplet combination in treating KRAS G12C mutant non-small cell
lung cancer.”
RAMP 203 Clinical Update
As of a November 21, 2024, data cutoff, three patients whose
cancer previously progressed on a G12C inhibitor have been treated
with the triplet combination of sotorasib 960 mg administered daily
on a continuous schedule and avutometinib 3.2 mg twice-weekly (BIW)
plus defactinib 200 mg twice-daily (BID). Avutometinib and
defactinib are administered on a three out of four weeks schedule.
Two of the three patients demonstrated initial tumor reductions of
at least 20% at the first scan. As of the data cutoff, all three
patients remain on treatment. With no DLTs observed in the first
triplet combination cohort, the Company anticipates the enrollment
of additional patients to the triplet combination prior to
presenting the data at a medical meeting next year.
As previously reported, the doublet combination of avutometinib
with sotorasib has completed enrollment (n=28) in the G12C
inhibitor treatment-naïve Stage 1 Part B cohort. The KRAS G12C
inhibitor prior-treated Stage I Part B cohort is still enrolling
patients and is anticipated to complete enrollment in early 2025.
Patients in both cohorts continue to be followed for safety and
efficacy to determine if observed efficacy supports expanded
enrollment. The Company plans to complete enrollment and evaluate
the safety and efficacy of the triplet combination, before
expanding either of the doublet cohorts.
“We are encouraged by the initial data from the triplet
combination of avutometinib and sotorasib plus defactinib in the
RAMP 203 trial, which shows early evidence of tumor reductions for
patients who have limited treatment options,” said John Hayslip,
M.D., chief medical officer at Verastem Oncology. “While the data
matures for the doublet combination across cohorts, we are now
focused on completing the enrollment in the triplet combination,
guided by preclinical data that indicates that the addition of a
FAK inhibitor increases the anti-tumor efficacy of avutometinib
plus sotorasib in KRAS G12C mutant NSCLC models, and tumors that
progress on a G12C-inhibitor treatment can be made to respond again
upon treatment with a FAK inhibitor plus avutometinib. As planned,
the triplet combination builds on the experience from the RAMP 201
study in recurrent low-grade serous ovarian cancer, where there was
a clear advantage to adding defactinib. Based on the RAMP 201
results, we did an assessment of our clinical programs and made the
decision to add defactinib to almost all our studies.”
About RAMP 203
RAMP 203 is a Phase 1/2, multicenter, open label, dose
evaluation/expansion study evaluating the efficacy and safety of
avutometinib and sotorasib with or without defactinib in patients
with KRAS G12C mutant non-small cell lung cancer (NSCLC) who have
not been previously treated with a KRAS G12C inhibitor as well as
in patients who have been previously treated with a KRAS G12C
inhibitor (NCT05074810). RAMP 203 is being conducted in
collaboration with Amgen.
About the Avutometinib and Defactinib Combination
Avutometinib is an oral RAF/MEK clamp that potentially inhibits
MEK1/2 kinase activities and induces inactive complexes of MEK with
ARAF, BRAF, and CRAF potentially creating a more complete and
durable anti-tumor response through maximal RAS/MAPK pathway
inhibition. In contrast to currently available MEK-only inhibitors,
avutometinib blocks both MEK kinase activity and the ability of RAF
to phosphorylate MEK. This unique mechanism allows avutometinib to
block MEK signaling without the compensatory activation of MEK that
appears to limit the efficacy of the MEK-only inhibitors.
Defactinib is an oral, selective inhibitor of focal adhesion
kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2), the two
members of the focal adhesion kinase family of non-receptor protein
tyrosine kinases. FAK and Pyk2 integrate signals from integrin and
growth factor receptors to regulate cell proliferation, survival,
migration, and invasion. FAK activation has been shown to mediate
resistance to multiple anti-cancer agents including RAF and MEK
inhibitors.
Verastem Oncology is currently conducting clinical trials with
avutometinib with and without defactinib in RAS/MAPK driven tumors
as part of its Raf And Mek Program or RAMP. Verastem is currently
enrolling patients and activating sites for RAMP 301
(GOG-3097;ENGOT-ov81/NCRI) (NCT06072781) an international Phase 3
confirmatory trial evaluating the combination of avutometinib and
defactinib versus standard chemotherapy or hormonal therapy for the
treatment of recurrent low-grade serous ovarian cancer (LGSOC).
Verastem completed its rolling New Drug Application (NDA)
submission to the to the U.S. Food and Drug Administration (FDA),
for the investigational combination of avutometinib and defactinib
in adults with recurrent KRAS mutant LGSOC who received at least
one prior systemic therapy, in October 2024. The FDA granted
Breakthrough Therapy Designation for the treatment of patients with
recurrent LGSOC after one or more prior lines of therapy, including
platinum-based chemotherapy. Avutometinib alone or in combination
with defactinib was also granted Orphan Drug Designation by the FDA
for the treatment of LGSOC.
Verastem Oncology has established a clinical collaboration with
Amgen to evaluate LUMAKRAS™ (sotorasib) in combination with
avutometinib and defactinib in both treatment-naïve patients and in
patients whose cancer progressed on a G12C inhibitor as part of the
RAMP 203 trial (NCT05074810). Verastem has received Fast Track
Designation from the FDA for the triplet combination in April 2024.
RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating
avutometinib and defactinib with gemcitabine/nab-paclitaxel in
patients with front-line metastatic pancreatic cancer, is supported
by the PanCAN Therapeutic Accelerator Award. FDA granted Orphan
Drug Designation to the avutometinib and defactinib combination for
the treatment of pancreatic cancer.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development
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 RAS/MAPK-driven
cancers, specifically novel small molecule drugs that inhibit
critical signaling pathways in cancer that promote cancer cell
survival and tumor growth, including RAF/MEK inhibition and FAK
inhibition. For more information, please visit www.verastem.com and
follow us on LinkedIn.
Forward Looking Statements
This press release includes forward-looking statements about,
among other things, Verastem Oncology’s programs and product
candidates, strategy, future plans and prospects, including
statements related to, the expected additional enrollment and
expansion of cohorts in the Company’s RAMP 203 trial, the expected
timing of the presentation of updated RAMP 203 data by the Company,
and the potential clinical value of various of the Company’s
clinical trials, including the RAMP 203 trial. 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.
Forward-looking statements are not guarantees of future
performance and are subject to risks and uncertainties that could
cause our actual results to differ materially from those expressed
or implied in the forward-looking statements we make. 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
avutometinib in combination with other compounds, including
defactinib, LUMAKRAS™ and others; the uncertainties inherent in
research and development, such as negative or unexpected results of
clinical trials, the occurrence or timing of applications for our
product candidates that may be filed with regulatory authorities in
any jurisdictions; whether and when regulatory authorities in any
jurisdictions may approve any such applications that may be filed
for our product candidates, and, if approved, whether our product
candidates will be commercially successful in such jurisdictions;
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 trial design, labeling and other
matters that could affect the timing, 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 the
market opportunities of our drug candidates are based on internal
and third-party estimates which may prove to be incorrect; 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,
which may delay our development programs, including delays in
review by the FDA of our NDA submission in recurrent KRAS mutant
LGSOC if enrollment in our confirmatory trial is not well underway
at the time of submission, or that the FDA may require the Company
to have completed enrollment or to enroll additional patients in
the Company’s ongoing RAMP-301 confirmatory Phase 3 clinical trial
prior to the FDA taking action on our NDA seeking accelerated
approval; risks associated with preliminary and interim data, which
may not be representative of more mature data, including with
respect to interim duration of therapy data; that our product
candidates will cause adverse safety events and/or unexpected
concerns may arise from additional data or analysis, or result in
unmanageable safety profiles as compared to their levels of
efficacy; that we may be unable to successfully validate, develop
and obtain regulatory approval for companion diagnostic tests for
our product candidates that require or would commercially benefit
from such tests, or experience significant delays in doing so; that
the mature RAMP 201 data and associated discussions with the FDA
may not support the scope of our NDA submission for the
avutometinib and defactinib combination in LGSOC, including with
respect to KRAS wild type LGSOC; that our product candidates may
experience manufacturing or supply interruptions or failures; that
any of our third party contract research organizations, contract
manufacturing organizations, clinical sites, or contractors, among
others, who we rely on fail to fully perform; that we face
substantial competition, which may result in others developing or
commercializing products before or more successfully than we do
which could result in reduced market share or market potential for
our product candidates; 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, including as a result of conducting
additional studies or our decisions regarding execution of such
commercialization; that we may not have sufficient cash to fund our
contemplated operations, including certain of our product
development programs; that we may not attract and retain high
quality personnel; that we or Chugai Pharmaceutical Co., Ltd. will
fail to fully perform under the avutometinib license agreement;
that the total addressable and target markets for our product
candidates might be smaller than we are presently estimating; that
we or Secura Bio, Inc. (Secura) will fail to fully perform under
the asset purchase agreement with Secura, including in relation to
milestone payments; that we will not see a return on investment on
the payments we have and may continue to make pursuant to the
collaboration and option agreement with GenFleet Therapeutics
(Shanghai), Inc. (GenFleet), or that GenFleet will fail to fully
perform under the agreement; that we may not be able to establish
new or expand on existing collaborations or partnerships, including
with respect to in-licensing of our product candidates, on
favorable terms, or at all; that we may be unable to obtain
adequate financing in the future through product licensing,
co-promotional arrangements, public or private equity, debt
financing or otherwise; 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, 2023 as filed with the Securities
and Exchange Commission (SEC) on March 14, 2024 and in any
subsequent filings with the SEC, which are available at
www.sec.gov. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241218222756/en/
For Investor and Media Inquiries: Julissa Viana Vice
President, Corporate Communications and Investor Relations
investors@verastem.com or media@verastem.com
Verastem (NASDAQ:VSTM)
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Verastem (NASDAQ:VSTM)
過去 株価チャート
から 1 2024 まで 1 2025
