Recurrent low-grade serous ovarian cancer is a
rare cancer with no FDA-approved treatments
Company seeking accelerated approval and
priority review of its NDA submission in patients with KRAS mutant
low-grade serous ovarian cancer; FDA filing decision expected
before the end of 2024 with potential for FDA approval decision by
mid-2025
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced that the Company has completed its rolling New Drug
Application (NDA) to the U.S. Food and Drug Administration (FDA)
for the investigational and potential first-in-class combination of
avutometinib, an oral RAF/MEK clamp, and defactinib, an oral
selective FAK inhibitor, for adults with recurrent KRAS mutant
low-grade serous ovarian cancer (LGSOC), who received at least one
prior systemic therapy.
There are currently no FDA-approved treatments specifically for
LGSOC, a rare and distinct ovarian cancer that differs from
high-grade serous ovarian cancer in both its biology and behavior.
Verastem submitted the NDA under the FDA’s Accelerated Approval
pathway and requested a Priority Review based on the combination’s
potential to address significant unmet medical need among patients
with recurrent LGSOC. If granted, the FDA review will be completed
within six months following the 60-day filing period. If approved,
Verastem expects that avutometinib plus defactinib will be the
first-ever FDA-approved treatment specifically for adult patients
in the United States with recurrent KRAS mutant LGSOC.
“We believe that avutometinib in combination with defactinib has
the potential to change the treatment paradigm for patients with
recurrent KRAS mutant low-grade serous ovarian cancer,” said Dan
Paterson, president and chief executive officer of Verastem
Oncology. “Completing our NDA submission is a significant milestone
not only for Verastem as we plan for potential FDA approval in
mid-2025, but also for patients as there are no FDA-approved
treatments specifically for this rare ovarian cancer.”
The Company initiated the rolling NDA submission in May 2024
after reviewing preliminary data with the FDA. Updated results from
the Phase 2 registration-directed RAMP 201 study were presented in
a late-breaking oral plenary presentation at the International
Gynecologic Cancer Society 2024 Annual Meeting and demonstrated in
patients with KRAS mutant LGSOC, a confirmed overall response rate
(ORR) of 44%, a median progression free survival (PFS) of 22
months, and a disease control rate at 6 months of 70%. The updated
data continue to demonstrate avutometinib in combination with
defactinib is generally well-tolerated, with a 10% discontinuation
rate due to adverse events (AEs) across all patients (both KRAS
mutant and KRAS wild-type). The NDA submission also includes
supportive data from the FRAME Phase 1 trial, the first study
conducted with the combination in recurrent LGSOC.
The FDA previously granted Breakthrough Therapy Designation for
avutometinib plus defactinib 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.
The Company is currently enrolling patients with recurrent LGSOC
regardless of KRAS mutation status for RAMP 301, an international
Phase 3 trial, which will serve as a confirmatory study for the
initial indication and has potential to support an expanded
indication regardless of KRAS mutation status.
About RAMP 201
RAMP 201 (ENGOTov60/GOG3052) is an adaptive, two-part
multicenter, parallel cohort, randomized, open-label trial to
evaluate the efficacy and safety of avutometinib alone and in
combination with defactinib in patients with recurrent low-grade
serous ovarian cancer. The first part of the study (Part A)
determined the selection of the go forward regimen, which was the
combination of avutometinib and defactinib versus avutometinib
alone, based on overall response rates. The expansion phases of the
trial (Parts B and C) are evaluating the safety and efficacy of the
go forward regimen of avutometinib 3.2 mg twice weekly and
defactinib 200 mg twice daily. The Part D portion of the trial is
evaluating a low dose of avutometinib in combination with
defactinib to inform individualized dose reduction.
About Low-Grade Serous Ovarian Cancer (LGSOC)
LGSOC is a rare ovarian cancer that is insidious, persistent and
ultimately fatal. LGSOC is distinct and different from high-grade
serous ovarian cancer (HGSOC) and requires different treatment.
LGSOC is highly recurrent and less sensitive to chemotherapy
compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and
80,000 worldwide are living with this disease. LGSOC affects
younger women with bimodal peaks of diagnosis at ages between 20-30
and 50-60 and has a median survival of approximately ten years. The
majority of patients report a negative impact of LGSOC on their
mental and physical health, fertility, and long-term quality of
life. The current standard of care for this disease includes
hormone therapy and chemotherapy, but there are no treatments
specifically approved by the U.S. Food and Drug Administration to
treat LGSOC.
About the Avutometinib and Defactinib Combination
Avutometinib is a RAF/MEK clamp that 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 other
MEK-only inhibitors.
Verastem Oncology is currently conducting clinical trials with
avutometinib 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 (NCT06072781)
an international Phase 3 confirmatory trial evaluating the
combination of avutometinib and defactinib, a selective FAK
inhibitor, versus standard chemotherapy or hormonal therapy for the
treatment of recurrent low-grade serous ovarian cancer (LGSOC).
RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of
avutometinib in combination with defactinib in patients with
recurrent LGSOC and enrollment has been completed for the RAMP 201
trial.
Verastem completed its rolling New Drug Application (NDA)
submission 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, with a potential FDA
decision mid-2025. The FDA granted Breakthrough Therapy Designation
of the investigational combination of avutometinib and defactinib
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 clinical collaborations with
Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) in combination
with avutometinib and defactinib and KRAZATI™ (adagrasib) in
combination with avutometinib in KRAS G12C mutant NSCLC as part of
the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials,
respectively. The 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
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 timing for the FDA review of the
NDA submission for the avutometinib and defactinib combination in
LGSOC, the ongoing discussions with the FDA and the ability to
obtain Accelerated Approval and Priority Review of the mature RAMP
201 data, the potential of the combination of avutometinib and
defactinib to change the way patients with recurrent LGSOC are
treated, the potential of the results of the RAMP 301 Phase 3 trial
to expand the indication regardless of KRAS mutation status, the
structure of our planned and pending clinical trials, the potential
clinical value of various of the Company’s clinical trials,
including the RAMP 201, RAMP 205 and RAMP 301 trials, interactions
with regulators, the timeline and indications for clinical
development, regulatory submissions and the potential for and
timing of commercialization of product candidates. 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 enroll additional patients in the Company’s ongoing RAMP-301
confirmatory Phase 3 clinical trial prior to 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20241031747822/en/
For Investor and Media Inquiries: Julissa Viana Vice
President, Corporate Communications and Investor Relations
investors@verastem.com or media@verastem.com
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