Data Build on Breakthrough Therapy Designation
of the Combination of Avutometinib and Defactinib in Low-Grade
Serous Ovarian Cancer
Clinically Meaningful Response Rates and
Manageable Safety and Tolerability Profile Continue to be
Demonstrated in Heavily Pretreated Patient Population Regardless of
KRAS Status
Results to Be Presented in a Poster Discussion
Session at the American Society of Clinical Oncology Annual
Meeting
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced updated data from Part A of the ongoing
registration-directed RAMP 201 (ENGOTov60/GOG3052) trial evaluating
the safety and efficacy of avutometinib (VS-6766) alone and in
combination with defactinib among patients with recurrent low-grade
serous ovarian cancer (LGSOC).
In the RAMP 201 study, treatment with the combination of
avutometinib and defactinib resulted in an objective response rate
(ORR) of 45% (13/29) and tumor shrinkage in 86% (25/29) of
evaluable patients. Safety and tolerability continued to be
favorable and consistent with previously reported data. These data,
which will be presented at the American Society of Clinical
Oncology Annual Meeting, build on the Breakthrough Therapy
Designation granted by the U.S. Food and Drug Administration (FDA)
for the combination in recurrent LGSOC.
RAMP 201 is an international registration-directed Phase 2 study
evaluating the safety and efficacy of avutometinib (VS-6766) alone
and in combination with defactinib among patients with recurrent
LGSOC. The key objectives of Part A (Selection Phase) of the RAMP
201 LGSOC study were to select avutometinib monotherapy or the
combination of avutometinib and defactinib as the go forward
regimen to be studied in Part B (Expansion Phase) of the study, and
to assess efficacy in both KRAS mutant and KRAS wild type LGSOC.
These data reinforce the selection of the combination of
avutometinib (3.2 mg PO twice weekly 21/28 days) with defactinib
(200 mg PO BID 21/28 days) as the go forward regimen regardless of
KRAS status, and target enrollment has been achieved in both Part A
and Part B.
“These results demonstrate avutometinib in combination with
defactinib can deliver high response rates for patients with
recurrent LGSOC with a promising safety profile to date,” said Dr.
Susana Banerjee, MBBS, MA PhD, FRCP, global and 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. “It is particularly
encouraging to see extensive tumor shrinkage in women who have had
several treatment lines, including prior MEK inhibitors. These
latest findings suggest the combination may offer a new treatment
option for women with this hard-to-treat cancer, and we are hopeful
it will become the new standard of care.”
Updated Results of Avutometinib and Defactinib Combination in
RAMP 201 Part A
In Part A of the RAMP 201 trial, 31 patients with recurrent
LGSOC were treated with the combination of avutometinib and
defactinib, of which 29 were evaluable for efficacy with a minimum
follow-up of 12 months and 13 patients remain on study
treatment.
Overall, patients were heavily pretreated with a median of 4
prior systemic regimens (up to 11), including prior platinum-based
chemotherapy, endocrine therapy and bevacizumab in most patients
and prior MEK inhibitor therapy in about 13% of patients. Confirmed
objective response rates (ORR) by blinded independent central
review of 45% (13/29; 95% CI: 26%-64%) were observed. Tumor
shrinkage was observed in the majority of patients, 86% (25/29).
Further, 3 out of 4 patients who received prior MEK inhibitors
responded to the combination.
Among the patients with KRAS mutant LGSOC, the ORR was 60%
(9/15) in the combination arm. Among the patients with KRAS wild
type LGSOC, the ORR was 29% (4/14). The median time to response was
5.5 months (range 1.6-14.7 months). The median duration of response
and median progression free survival have not been reached.
The safety profile was consistent with previously reported
safety data. The most common treatment-related adverse events for
the combination in all treated patients (n=81) were nausea and
vomiting, diarrhea, blood creatine phosphokinase (CPK) increased,
peripheral edema, vision blurred, dermatitis acneiform and rash,
fatigue, and dry skin, most of which were mild to moderate. The
discontinuation rate, due to ≥ 1 adverse event, was 12% in the
trial overall to date (4.9% due to elevated blood CPK).
“There are currently no treatments that are FDA or EMA approved
specifically for the treatment of LGSOC, and this is clearly an
area of unmet need. These results indicate that the combination of
avutometinib and defactinib shows promise as a tolerable treatment
with impressive response rates for women with recurrent LGSOC.
Importantly, high response rates were seen both in women with and
without KRAS mutations,” said Rachel N. Grisham, M.D., Section
Head, Ovarian Cancer and Director, Westchester Gynecologic Medical
Oncology at Memorial Sloan Kettering Cancer Center NY, and the
study’s principal US investigator. “We look forward to the future
outcomes from this important trial and improving care for women
with LGSOC.”
Regulatory Update
The Company plans to include mature data from RAMP 201, the
Verastem sponsored clinical trial, and the investigator-sponsored
FRAME study to support filing for accelerated approval. The Company
is finalizing the design of a randomized confirmatory trial with
the FDA, which is planned to begin in the second half of 2023.
Dr. Banerjee and Dr. Grisham have consulting relationships with
Verastem Oncology.
About Avutometinib (VS-6766)
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
pathway inhibition. Avutometinib is currently in late-stage
development.
In contrast to other MEK 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 inhibitors. The U.S. Food and Drug
Administration granted Breakthrough Therapy designation for the
combination of Verastem Oncology’s investigational RAF/MEK clamp
avutometinib, with defactinib, its 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.
Verastem Oncology is currently conducting clinical trials with
its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part
of its (Raf And Mek Program). RAMP 201
is a registration-directed trial of avutometinib alone and in
combination with defactinib in patients with recurrent LGSOC.
Verastem Oncology has established clinical collaborations with
Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and KRAZATI™
(adagrasib) in combination with avutometinib in KRAS G12C mutant
NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively.
Supported by the “Therapeutic Accelerator Award” Verastem Oncology
received from PanCAN, the Company is conducting RAMP 205, a Phase
1b/2 clinical trial evaluating avutometinib and defactinib with
gemcitabine/nab-paclitaxel in patients with front-line metastatic
pancreatic cancer.
About Low-Grade Serous Ovarian Cancer (LGSOC)
LGSOC is a highly recurrent, chemotherapy-resistant cancer,
associated with slow tumor growth and high mortality rate.
Approximately 6,000 women in the U.S. and 80,000 worldwide are
living with this disease. Mutations in the KRAS gene are present in
30% of cases of LGSOC. LGSOC is most often diagnosed in women
between the ages of 45-55 years and has a median survival of
approximately ten years. The majority of patients experience severe
pain and complications as the disease progresses. Chemotherapy is
the standard of care for this disease, with limited treatment
options currently available.
About RAMP 201
Verastem Oncology has initiated a Phase 2 registration-directed
trial evaluating avutometinib alone and in combination with
defactinib in patients with recurrent LGSOC as part of RAMP
(Raf And Mek Program). RAMP 201
(ENGOTov60/GOG3052) is an international collaboration between the
European Network of Gynaecological Oncological Trial groups (ENGOT)
and the Gynecologic Oncology Group (GOG) and sponsored by Verastem
Oncology. It 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 LGSOC. The first part of the study will determine
the optimal regimen of either avutometinib monotherapy or in
combination with defactinib in patients with recurrent LGSOC
randomized 1:1 in each treatment arm. The determination of which
regimen to take forward into the expansion phase of the trial will
be made based on objective response rate data. The expansion phase
of the study will examine efficacy and safety parameters of the
regimen selected.
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.
About The GOG Foundation, Inc. (www.gog.org)
The GOG Foundation, Inc. is a not-for-profit organization with
the purpose of promoting excellence in the quality and integrity of
clinical and translational scientific research in the field of
gynecologic malignancies. The GOG Foundation is committed to
maintaining the highest standards in clinical trials development,
execution, analysis, and distribution of results. The GOG
Foundation is the only clinical trialist group in the United States
that focuses its research on patients with pelvic malignancies,
such as cancer of the ovary (including surface peritoneal
malignancies), uterus (including endometrium, soft tissue sarcoma,
and gestational trophoblastic neoplasia), cervix, and vulva. The
GOG Foundation is multi-disciplinary in its approach to clinical
trials, and includes gynecologic oncologists, medical oncologists,
pathologists, radiation oncologists, oncology nurses,
biostatisticians (including those with expertise in
bioinformatics), basic scientists, quality of life experts, data
managers, and administrative personnel.
About the GOG Partners Program
Supported by industry, GOG Partners program is structured to
work directly with pharmaceutical organizations and operate
clinical trials outside the National Cancer Institute (NCI)
framework. The GOG Partners program promotes the mission of the GOG
Foundation dedicated to transforming the care in Gynecologic
Oncology. By providing an alternative venue for patient accrual and
site infrastructure support, GOG Partners has helped provide
additional trials and opportunities for patients outside the
national gynecologic clinical trials network.
About ENGOT (www.engot.esgo.org)
The European Network for Gynaecological Oncological Trial
(ENGOT) groups is a research network of the European Society of
Gynaecological Oncology and was founded in Berlin in October 2007.
Currently, ENGOT consists of 21 trial groups from 31 European
countries that perform cooperative clinical trials. ENGOT’s
ultimate goal is to bring the best treatment to gynecological
cancer patients through the best science and enabling every patient
in every European country to access a clinical trial.
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 various of
its clinical trials, the timing of commencing and completing
trials, including topline data reports, interactions with
regulators 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. 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 avutometinib in combination with other
compounds, including defactinib, LUMAKRASTM and others; 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 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
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, including as a result of conducting
additional studies; that we or Chugai Pharmaceutical Co., Ltd. will
fail to fully perform under the avutometinib license agreement;
that we or our other collaboration partners may fail to perform
under our collaboration agreements; that we may not have sufficient
cash to fund our contemplated operations; 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 Secura Bio, Inc. will achieve the
milestones that result in payments to us under our asset purchase
agreement with Secura Bio, Inc.; that we will be unable to execute
on our partnering strategies for avutometinib in combination with
other compounds; 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, 2022 as filed with the Securities
and Exchange Commission (SEC) on March 14, 2023 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20230525005738/en/
Investors: Dan Calkins +1 781-469-1694 Investor Relations
dcalkins@verastem.com
Nate LiaBraaten +1 212-600-1902 nate@argotpartners.com
Media: Lisa Buffington Corporate Communications +1
781-292-4205 lbuffington@verastem.com
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