Plan to complete NDA submission with the mature
RAMP 201 dataset, anticipated to include 12 months of follow-up, in
the second half of 2024
Plan to present the mature dataset from RAMP
201 at a medical conference in the second half of 2024
Avutometinib and defactinib combination have
continued to show robust and durable response rates in ongoing RAMP
201 trial in patients with recurrent low-grade serous ovarian
cancer
Company to host investor conference call and
webcast on Friday, May 24, 2024 at 8:00 am EDT to provide update on
RAMP 201 and rolling NDA submission
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced that it has initiated the rolling submission of a
New Drug Application (NDA) to the U.S. Food and Drug Administration
(FDA) seeking accelerated approval of the combination of
avutometinib, a RAF/MEK clamp, and defactinib, a selective FAK
inhibitor, for adult patients with recurrent KRAS mutant (KRAS mt)
low-grade serous ovarian cancer (LGSOC), who received at least one
prior systemic therapy. The rolling review process allows the
Company to submit completed sections of an application for review
by the FDA before all sections become available. The initial
sections of the application will include the nonclinical and
quality sections. In discussions with the FDA, Verastem reached
agreement to submit a primary efficacy analysis based on the RAMP
201 study with 12 months of follow up. Based on discussions with
the FDA, we understand that the proposed indication for final
submission of the clinical module can be expanded in the event
Verastem provides data that demonstrates a substantial improvement
over available therapy in the KRAS wild-type (KRAS wt) population.
FDA has accepted Verastem’s plan to submit the clinical module in
the second half of 2024 to complete the NDA application.
Previously, the FDA granted Breakthrough Therapy Designation (BTD)
for the combination for treatment of patients with recurrent LGSOC,
regardless of KRAS status, following one or more previous lines of
therapy and Orphan Drug Designation (ODD) for the combination in
certain LGSOC indications. The Company plans to request a priority
review of the NDA. Currently, there are no FDA-approved treatments
specifically for recurrent LGSOC.
"The initiation of our rolling NDA submission of the
avutometinib and defactinib combination for accelerated approval,
is an important step towards addressing the significant unmet needs
that patients face living with KRAS mutant low-grade serous ovarian
cancer," said Dan Paterson, president and chief executive officer
of Verastem Oncology. "The data from our ongoing RAMP 201 trial
continues to support our belief that the avutometinib and
defactinib combination has the potential to be a new standard of
care in patients with recurrent low-grade serous ovarian cancer, if
approved. In the second half of this year, we anticipate completing
our NDA submission with the mature data from the RAMP 201 trial and
discussing with the FDA a path forward for patients with KRAS
wild-type disease. We also expect to present the mature dataset at
a medical meeting in the second half of 2024."
RAMP 201 is a Phase 2 registration-directed study evaluating
avutometinib and defactinib combination in patients with recurrent
LGSOC. The enrollment in RAMP 201 is completed, with 115 patients
being treated at the recommended Phase 2 dose (RP2D) of
avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily
for 3 out of every 4 weeks, and follow-up continues. Verastem
expects to complete the NDA submission after obtaining mature
safety and efficacy data from the RAMP 201 trial, including 12
months of follow-up, anticipated in the second half of 2024.
Verastem also plans to further discuss the KRAS wt data with FDA to
inform the potential path forward for approval for this patient
population. The Company plans to present the mature dataset from
RAMP 201 at a medical meeting in the second half of 2024. As of
February 2024, the interim data continued to show robust overall
response rates (ORR) and durable responses with low discontinuation
rates due to adverse events (AEs) in patients from RAMP 201 Parts
A, B, C, who had a minimum follow-up of five (5) months.
The FDA granted Breakthrough Therapy Designation of the
investigational combination of avutometinib and defactinib for the
treatment of all patients with recurrent LGSOC regardless of KRAS
status after one or more prior lines of therapy, including
platinum-based chemotherapy in May 2021. Avutometinib alone or in
combination with defactinib was also granted Orphan Drug
Designation by the FDA for the treatment of LGSOC in March 2024.
The Company believes that this Orphan Drug Designation signifies
that LGSOC is a rare ovarian cancer that is a distinct and
different disease from other forms of ovarian cancer such as
high-grade serous ovarian cancer (HGSOC). LGSOC is highly recurrent
and fatal, with no FDA-approved treatment options, and the current
standard of care treatments include hormonal therapy or
chemotherapy, which have demonstrated an ORR between 6-13% with
discontinuation due to AEs of 17-30%.
The Company is currently enrolling patients and activating sites
for RAMP 301, an international confirmatory Phase 3 trial,
evaluating the avutometinib and defactinib combination versus
standard of care chemotherapy or hormonal therapy for the treatment
of patients with KRAS mt and KRAS wt recurrent LGSOC.
Conference Call and Webcast Information
Verastem will hold an investor conference call and webcast on
Friday, May 24 at 8:00 am EDT, to review the initiation of the NDA
submission and limited, topline data from the RAMP 201 trial, with
a minimum follow-up of five (5) months and the RAMP 205 data. The
call will feature members of Verastem’s management team. To access
the conference call, please dial (844) 763-8274 (local) or (412)
717-9224 (international) at least 10 minutes prior to the start
time and ask to be joined into the Verastem Oncology conference
call. A live audio webcast of the call, along with accompany
slides, will be accessible here. The Company expects to file an 8-K
pertaining to this update.
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 RAMP 301
RAMP 301 (GOG-3097; ENGOT-ov81/NCRI) is an international
collaboration between The GOG Foundation, Inc. (GOG) and the
European Network of Gynaecological Oncological Trial groups (ENGOT)
sponsored by Verastem Oncology. The trial is expected to enroll a
total of 270 patients in the U.S., Canada, the United Kingdom,
Europe, Australia and South Korea, who will be randomized to either
the combination of avutometinib and defactinib or investigator’s
choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel,
topotecan) or hormone therapy (letrozole, anastrozole). The primary
endpoint is progression free survival (PFS) by Blinded Independent
Central Review. Secondary endpoints include ORR, duration of
response, disease control rate, safety and tolerability, patient
reported outcomes, and overall survival.
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 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 n investigational RAF/MEK clamp that is
designed to induce 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. Avutometinib
is designed to block both MEK kinase activity and the ability of
RAF to phosphorylate MEK. This differentiated proposed mechanism
potentially allows avutometinib to block MEK signaling without the
compensatory activation of MEK that appears to limit the efficacy
of other MEK-only inhibitors. The U.S. Food and Drug Administration
(FDA) granted Breakthrough Therapy Designation of the
investigational combination of avutometinib and defactinib, a
selective FAK inhibitor, for the treatment of all patients with
recurrent low-grade serous ovarian cancer (LGSOC) regardless of
KRAS status 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 is currently conducting clinical trials with
avutometinib in RAS/MAPK driven tumors as part of its Raf
And Mek Program or RAMP. RAMP 301
(NCT06072781) is an international Phase 3 confirmatory trial
evaluating the combination of avutometinib and defactinib versus
standard chemotherapy or hormonal therapy for the treatment of
recurrent 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 in each of the dose optimization and expansion phases and
the low-dose evaluation.
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 a PanCAN Therapeutic Accelerator
Award.
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 of the planned rolling
New Drug Application (NDA) submission for the avutometinib and
defactinib combination in low-grade serous ovarian cancer, the
potential clinical value of various of the Company’s clinical
trials, including the RAMP 201, RAMP 205 and RAMP 301 trials, the
timing of commencing and completing trials, including topline data
reports, interactions with regulators, the potential for and timing
of commercialization of product candidates and potential for
additional development programs involving Verastem Oncology’s lead
compound. 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 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 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; 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 submission or review by
the FDA of our NDA submission in recurring 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 Verastem submitting or the FDA taking action on our NDA
seeking accelerated approval; 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 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; that we may
not have sufficient cash to fund our contemplated operations; 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 our target market for our
product candidates might be smaller than we are presently
estimating; that Secura Bio, Inc. will fail to fully perform under
the asset purchase agreement with Secura Bio, Inc., 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 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.
As a result of these and other factors, we may not achieve the
plans, intentions or expectations disclosed in our forward-looking
statements, and you should not place undue reliance on our
forward-looking statements. 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. 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/20240524990712/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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