Combination of Avutometinib with Defactinib
Declared as Go Forward Treatment Regimen in Low-Grade Serous
Ovarian Cancer (LGSOC) Program
Blinded Independently Confirmed Response Rates
in Both KRAS Mutant and KRAS Wild-Type Tumors and Favorable Safety
and Tolerability Profile Supports Continued Development in All
Recurrent LGSOC
Company Intends to File for Accelerated
Approval; Timing Based on Mature Data from RAMP 201 Study and
Finalization of Confirmatory Study Plans
Management to Host Conference Call Today at
6:00 PM ET
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announces positive interim data from Part A of the ongoing
RAMP 201 (ENGOTov60/GOG3052) 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 low-grade serous ovarian cancer (LGSOC). The Company
is also providing a regulatory update following a productive
meeting with the U.S. Food and Drug Administration (FDA).
“The interim data from the ongoing phase 2 RAMP 201 trial show
that the combination of avutometinib with defactinib yields
encouraging response rates with a well-tolerated safety profile in
women with heavily pre-treated recurrent low-grade serous ovarian
cancer,” said Dr. Susana Banerjee, MBBS, MA, PhD, FRCP, 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. “The
contribution of defactinib, rates of tumor shrinkage in both KRAS
mutant and KRAS wild-type LGSOC and a high disease control rate
seen so far are important initial findings leading to the decision
to move forward with the combination regimen. We look forward to
the final analysis.”
Results of RAMP 201 Part A Interim Analysis
The objective of Part A (selection phase) of the RAMP 201 LGSOC
study was to select the go forward regimen between avutometinib
monotherapy or the combination of avutometinib and defactinib to be
studied in Part B (expansion phase) of the study. In addition, the
efficacy was assessed in both KRAS mutant and KRAS wild type LGSOC.
Part A randomized eligible patients to avutometinib monotherapy
(n=33) or the combination of avutometinib and defactinib (n=31).
The combination of avutometinib and defactinib has been declared
the go forward treatment regimen based on a higher rate of
confirmed objective responses in a planned interim analysis with
prespecified criteria.
Overall, patients on the combination arm were heavily pretreated
with an average 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 20% of patients.
Of the 29 patients evaluable for response by blinded independent
central review (BICR) in the combination arm, the initial results
showed a confirmed objective response rate (ORR) of 28% in all
patients and 27% vs 29% in KRAS mutant (n=15) and KRAS wild-type
(n=14) LGSOC, respectively. Three additional patients with KRAS
mutant LGSOC showed an unconfirmed partial response. In addition,
the vast majority of patients showed tumor regression, as the
overall disease control rate (stable disease plus partial response)
was 93%. Most evaluable patients (62%) were still on study
treatment on the combination arm at the time of the data cut with a
minimum follow-up of 5 months.
The confirmed ORR for the monotherapy arm by BICR was 7% in
evaluable patients (n=30). The overall disease control rate for the
monotherapy arm by BICR was 90%.
Across both the combination and monotherapy arms, there have
been no additional safety signals reported with a continued
favorable safety and tolerability profile. The most common
treatment-related adverse events for the combination in all treated
patients were diarrhea, nausea, blood creatine phosphokinase (CPK)
increased, vision blurred, dermatitis acneiform and rash, fatigue
and peripheral edema, most of which were mild to moderate, with 9%
discontinuation due to adverse events.
“LGSOC is a difficult disease to treat and one in urgent need of
more effective and tolerable therapies. The majority of patients
with LGSOC present with advanced stage disease and experience
chronic symptoms from their cancer. Prior studies have shown
disappointing response rates with conventional chemotherapy or
hormonal therapy and there are currently no agents that are FDA
approved specifically for the treatment of this cancer,” 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. “The interim positive data from RAMP 201 are
encouraging and indicate the combination of avutometinib and
defactinib remains a promising approach for treating patients with
recurrent LGSOC.”
Target enrollment for the combination arm in RAMP 201 has been
achieved. The Company is planning a RAMP 201 presentation at a
scientific conference in mid-2023.
Regulatory Update Following Type B FDA Meeting on LGSOC
Program
A recent FDA meeting was held to discuss the encouraging results
to date of the ongoing RAMP 201 trial evaluating avutometinib ±
defactinib among patients with recurrent LGSOC, confirm the go
forward treatment regimen selection and discuss the regulatory path
forward. The combination of avutometinib with defactinib has been
selected vs monotherapy as the go forward treatment in all
recurrent LGSOC regardless of KRAS status, acknowledging the
demonstrated contribution of defactinib.
The Company intends to include mature data from RAMP 201, the
Verastem sponsored clinical trial, and the FRAME study, led by The
Institute of Cancer Research, London, and The Royal Marsden NHS
Foundation Trust to potentially support filing for accelerated
approval. Both studies are evaluating avutometinib and defactinib
in patients with recurrent LGSOC. The Company is in ongoing
discussions with the FDA on the confirmatory study and plans to
provide an update after agreement with the FDA. Continued
enrollment in the combination arm of RAMP 201 is planned to expand
the clinical experience in anticipation of initiation of a
confirmatory study.
“We appreciate the productive and ongoing discussions with the
FDA regarding the progress of our LGSOC program, including the
alignment around key next steps as part of our breakthrough therapy
designation,” said Brian Stuglik, CEO of Verastem Oncology. “With
the encouraging results of the RAMP 201 Part A interim analysis and
the FRAME study, we will work expeditiously to prepare to file for
an accelerated approval that encompasses the totality of the data
from both trials as well as progress on the confirmatory
study.”
Conference Call, Presentation and Webcast Information
The Verastem Oncology management team will host a conference
call and webcast today, Tuesday, January 24, 2023, at 6:00 PM ET.
The conference call can be accessed by clicking here. The webcast
of the conference call and accompanying slides can also be accessed
by visiting the investors section of the Company’s website at
www.verastem.com. A replay of the webcast will be archived on the
Company’s website for 90 days following the call.
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-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. As
part of 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.
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, LUMAKRAS™ 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, 2021 as filed with the Securities
and Exchange Commission (SEC) on March 28, 2022 and in the
Company’s Quarterly Reports on Form 10-Q for the quarters ended
June 30, 2022 and September 30, 2022, as filed with the SEC on
August 8, 2022 and November 3, 2022, respectively, 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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Investors:
Dan Calkins +1 781-469-1694 Investor Relations
dcalkins@verastem.com
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Media:
Lisa Buffington Corporate Communications +1 781-292-4205
lbuffington@verastem.com
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