Robust overall response rates observed (31%
overall, 44% in KRAS mutant, 17% in KRAS wild-type) in patients
whose cancer had progressed despite prior treatment with
chemotherapy and/or MEK inhibitors and/or bevacizumab
Patients on avutometinib and defactinib
achieved a median progression free survival of more than one year
(12.9 months); 22 months in KRAS mutant population
The Company recently met with the FDA to review
the mature data set and remains on track to complete the NDA
submission in October 2024
Additional data to be presented at the IGCS
meeting and during Company-hosted investor conference call and
webcast today, October 17, 2024 at 4:30 pm EDT
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced updated data from the Phase 2 RAMP 201
(ENGOTov60/GOG3052) clinical trial evaluating the combination of
avutometinib, an oral RAF/MEK clamp, and defactinib, an oral,
selective FAK inhibitor, in patients with recurrent low-grade
serous ovarian cancer (LGSOC). The data were published as a
late-breaking abstract and additional detailed findings will be
presented today in an oral plenary session at the International
Gynecologic Cancer Society (IGCS) 2024 Annual Meeting in Dublin,
Ireland.
The primary analysis of the RAMP 201 trial, with a data cutoff
of June 30, 2024, showed a confirmed overall response rate (ORR) by
blinded independent central review (BICR) of 31% (34/109; 95% CI:
23-41) in all evaluable patients with measurable disease with
approximately 12 months of follow up. Among patients with KRAS
mutant (mt) LGSOC, the confirmed ORR was 44% (25/57; 95% CI: 31-58)
and for patients with KRAS wild-type (wt) LGSOC the confirmed ORR
was 17% (9/52; 95% CI: 8-30). The median duration of response (DOR)
was 31.1 months (95% CI: 14.8-31.1) in all evaluable patients, with
31.1 months (95% CI: 14.8-31.1) in the KRAS mt population and 9.2
months (95% CI: 5.5-NEi) in the KRAS wt population. The median
progression-free survival (PFS) was 12.9 months (95% CI: 10.9-20.2)
in all evaluable patients, with 22 months (95% CI: 11.1-36.6) in
the KRAS mt population and 12.8 months (95% CI: 7.4-18.4) in the
KRAS wt population. The disease control rate (DCR) at 6 or more
months was 61% in the total evaluable population, 70% in KRAS mt
population and 50% in KRAS wt population. 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) and no new safety signals were identified. The
most common treatment-related AEs (all grades, grade ≥3) for the
combination were nausea (67.0%, 2.6%), diarrhea (58.3%, 7.8%), and
increased blood creatine phosphokinase levels (60.0%, 24.3%).
“The notable response rates and low discontinuation rate seen
with the combination of avutometinib and defactinib are
significant. These updated results confirm the potential of this
new combination therapy to change practice and be the new standard
for care for recurrent low-grade serous ovarian cancer, which
previously had limited effective treatment options,” said Professor
Susana Banerjee, M.B.B.S., M.A., Ph.D., F.R.C.P., Global Lead
investigator of the study, Consultant Medical Oncologist at The
Royal Marsden NHS Foundation Trust and Team Leader in Women’s
Cancers at The Institute of Cancer Research, London.
Regulatory Update
A Type A meeting was recently held with the U.S. Food and Drug
Administration (FDA), during which the Company aligned with the FDA
on the Company’s plans to complete the New Drug Application (NDA)
submission in October 2024 for adult patients with recurrent KRAS
mt LGSOC, who received at least one prior systemic therapy, based
on the mature data from the RAMP 201 trial. The Company plans to
seek Accelerated Approval from the FDA and request Priority Review.
At this time, the FDA did not recommend pursuing a KRAS wt
indication under Accelerated Approval. This strategic approach
allows the Company to potentially reach the market more efficiently
while mapping out a path forward with the FDA for the KRAS
wild-type indication, including leveraging data from the ongoing
RAMP 301 Phase 3 trial. RAMP 301, which is currently enrolling
patients with recurrent LGSOC regardless of KRAS mutation status,
will serve as a confirmatory study for the initial indication and
has potential to expand the indication regardless of KRAS mutation
status.
“In the mature data from the RAMP 201 trial most patients
achieved tumor reductions and a median progression-free survival
that was greater than one year across both KRAS mutant and KRAS
wild-type patient populations. These results reinforce our
confidence in the potential of the combination of avutometinib and
defactinib to change how patients with recurrent low-grade serous
ovarian cancer are treated,” said John Hayslip, M.D., chief medical
officer of Verastem Oncology. “Encouraged by the durable clinical
benefit seen in KRAS wild-type patients in RAMP 201 and the poorer
prognosis in this subset of patients that are treated with
sub-optimal treatment choices today, we believe that this treatment
combination will be the preferred treatment option for all
subgroups of patients with recurrent low-grade serous ovarian
cancer. We are committed to making the combination available to
these patients, including working with the FDA to outline a path
forward to expand the indication with additional data.”
“Now that we have the mature data from the RAMP 201 trial, we
are on track to complete our NDA submission for recurrent KRAS
mutant low-grade serous ovarian cancer in October,” said Dan
Paterson, president and chief executive officer of Verastem
Oncology. “We look forward to working with the FDA to potentially
bring the first and only FDA-approved treatment specifically for
patients with recurrent KRAS mutant low-grade serous ovarian cancer
to the U.S. market in 2025.”
Conference Call and Webcast Information
Verastem will hold an investor conference call and webcast on
October 17, 2024 at 4:30 p.m. EDT, to review the mature data from
the RAMP 201 trial. 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 accompanying slides, will be accessible under
“Events & Presentations” in the Investors & Media section
of the company’s website at www.verastem.com.
The Company expects to file a current report on Form 8-K with
the Securities and Exchange Commission (SEC) later today, which
will include a copy of the IGCS oral presentation and the
presentation which the Company intends to use on the investor
conference call and webcast.
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 initiated a rolling New Drug Application (NDA)
submission in May 2024 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 and expects to complete its NDA
submission in the second half of 2024 with a potential FDA decision
in the first half of 2025. The FDA granted Breakthrough Therapy
Designation of the investigational combination of avutometinib and
defactinib for the treatment of all 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 scope and expecting timing for the
completion 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, the timing of commencing and
completing trials, including topline data reports, 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
submission or 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
Verastem submitting or 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 rolling 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.
i NE = could not be estimated based on number of patients with
loss of response
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version on businesswire.com: https://www.businesswire.com/news/home/20241016127866/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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