RAMP 301 Is Evaluating the Combination of
Avutometinib and Defactinib vs Investigator’s Choice of Therapy
Reported Data from Part A of RAMP 201 Trial
Show an Objective Response Rate of 45%, and Manageable Safety and
Tolerability Profile with the Combination
Company Intends to Submit an Accelerated
Approval New Drug Application to the U.S. Food and Drug
Administration for the Combination Based on Breakthrough Therapy
Designation and Mature Data from RAMP 201 and FRAME Trials
Verastem Oncology (Nasdaq: VSTM) (the “Company”), a
biopharmaceutical company committed to advancing new medicines for
patients with cancer, announced today that it has initiated its
international confirmatory Phase 3 RAMP 301 trial (GOG-3097;
ENGOT-ov81/NCRI), evaluating the combination of avutometinib and
defactinib versus standard chemotherapy or hormonal therapy for the
treatment of recurrent low-grade serous ovarian cancer (LGSOC).
“Patients and treating physicians have advocated for more
research and development in support of LGSOC. At Verastem Oncology,
we are moving with urgency to offer a Phase 3 study specifically
directed at this disease in an effort to address this need,” said
Dan Paterson, President and Chief Executive Officer, Verastem
Oncology. “Based on our Breakthrough Therapy Designation, the
initiation and expected progress of this trial, along with the
FRAME study data and mature RAMP 201 data, we plan to file for
Accelerated Approval in the first half of next year, moving us a
significant step closer to addressing the treatment needs of
patients living with LGSOC.”
RAMP 301 is the confirmatory study required by the U.S. Food and
Drug Administration (FDA) for the combination of avutometinib and
defactinib to potentially receive full approval for the treatment
of recurrent LGSOC. The Company intends to submit an Accelerated
Approval New Drug Application (NDA) for the combination of
avutometinib and defactinib based on mature data from the Company’s
Phase 2 registration-directed RAMP 201 trial, together with the
results of the investigator-initiated FRAME trial. The company
recently reported results of Part A of the RAMP 201 trial,
including confirmed objective response rates (ORR) by blinded
independent central review of 45% with a response rate and safety
profile consistent with previous studies.
“LGSOC has a unique molecular, histologic, and clinical profile
that differs dramatically from the most common type of ovarian
cancer. Response rates to standard of care treatments are
disappointing, and there are still no FDA approved treatments
specifically for LGSOC,” said Rachel Grisham, M.D., Section Head,
Ovarian Cancer and Director, Gynecologic Medical Oncology at
Memorial Sloan Kettering Cancer Center in Westchester, NY and RAMP
301 global lead investigator. “The combination of avutometinib and
defactinib continues to show promise in recurrent LGSOC, and I am
looking forward to leading this confirmatory trial with the goal of
establishing a new standard of care for people with this rare form
of ovarian cancer.”
According to Professor Susana Banerjee, MBBS, MA, PhD, FRCP,
Consultant Medical Oncologist and Research Lead for the Gynaecology
Unit at The Royal Marsden NHS Foundation Trust, Team Leader in
Women's Cancers at The Institute of Cancer Research, London, and
lead European investigator of the RAMP 301 trial, “Based on my
experience treating women with LGSOC, it’s clear that we need
better therapeutic options. I am pleased this Phase 3 trial,
following the initial positive results from the Phase 2 RAMP 201
trial, is enrolling patients to potentially address the significant
limitations we have seen with other available therapies.”
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 270
patients 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. RAMP 301 is a global trial with
enrollment open in the U.S. and planned enrollment in Canada, the
United Kingdom, Europe, Australia, and Korea.
Dr. Grisham and Dr. Banerjee are paid consultants for Verastem
Oncology.
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
pathway inhibition. In contrast to currently available 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 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 301
is a 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 is
a Phase 2 registration-directed trial of avutometinib in
combination with defactinib in patients with recurrent LGSOC and
has completed enrollment in the dose optimization and expansion
phases and is enrolling for low-dose evaluation. 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
35-57% 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 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 standard of 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 and the timing of commencing and completing
trials and regulatory submissions. 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, 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 labeling and other matters that could affect
the 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 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 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.
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/20231213489476/en/
Investors: Ryan Porter Argot Partners +1 212-600-1902
ryan.porter@argotpartners.com Media: Lisa Buffington
Corporate Communications +1 781-292-4502
lbuffington@verastem.com
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