Avutometinib + Sotorasib Combination
Demonstrated Preliminary Efficacy with Confirmed Responses in both
KRAS G12C Inhibitor Resistant and Naïve Patients
No New Safety Signals Observed in Combination;
Most Treatment-Related Adverse Events Mild to Moderate
Enrollment of Patients Naïve to or Previously
Treated with a KRAS G12C Inhibitor Ongoing in Expansion Phase
Verastem Oncology (Nasdaq: VSTM) (the “Company”), a
biopharmaceutical company committed to advancing new medicines for
patients with cancer, announced today the initial safety,
pharmacokinetics and recommended Phase 2 dose (RP2D) in the RAMP
203 trial evaluating the safety, tolerability and efficacy of
avutometinib in combination with sotorasib in patients with KRAS
G12C-mutant non-small cell lung cancer (NSCLC). The results will be
presented at the AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics October 11-15, 2023 in
Boston, Massachusetts.
“The RAMP 203 study is investigating the potential benefits of a
more complete vertical blockade of the RAS pathway with the
combination of avutometinib and sotorasib in KRAS G12C-mutant
locally advanced or metastatic NSCLC,” said Mark Awad, M.D.,
Associate Professor of Medicine at Harvard Medical School and
Director of Clinical Research of the Lowe Center for Thoracic
Oncology at the Dana-Farber Cancer Institute, investigator on the
trial, and presenting author. “These initial findings, including
the recommended Phase 2 dose and the encouraging preliminary
efficacy and safety results, provide support for the combination,
and I look forward to completing the expansion phase of the
trial.”
RAMP 203 (NCT05074810) is a Phase 1/2, multicenter, open label,
dose evaluation/expansion study evaluating the efficacy and safety
of avutometinib + sotorasib in patients with KRAS G12C-mutant NSCLC
who have not been previously treated with a KRAS G12C inhibitor as
well as in patients who have been previously treated with a KRAS
G12C inhibitor. The confirmed objective response rate (ORR) was 25%
(3/12) across efficacy-evaluable patients and seen in both KRAS
G12C inhibitor resistant (14.3%; 1/7) and naïve (40%; 2/5)
patients.
The pharmacokinetic profile of avutometinib in combination with
sotorasib was similar to results in monotherapy studies. No
drug-drug interactions were observed between avutometinib and
sotorasib. Avutometinib 4.0 mg PO BIW 21/28 days + sotorasib 960 mg
PO QD 28/28 days was selected as RP2D based on dose limiting
toxicity (DLT) assessment. Enrollment of patients with KRAS
G12C-mutant NSCLC who are either naïve to or previously treated
with a KRAS G12C inhibitor is ongoing in the expansion phase of
RAMP 203.
“The RAMP 203 trial builds on preclinical data which
demonstrated the addition of avutometinib to sotorasib improved the
depth of MAPK pathway inhibition and substantially enhanced tumor
regression relative to sotorasib alone,” said Dan Paterson,
President and CEO, Verastem Oncology. “Given KRAS G12C mutations
are the most common KRAS mutation in NSCLC and acquired mutations
and amplifications occur upon clinical progression to KRAS G12C
inhibitor monotherapy, the results of the RAMP 203 trial are
important in understanding potential new treatment approaches for
patients.”
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 increased 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 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). 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 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 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 we may not attract and retain high quality
personnel; 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 our target market for our product
candidates might be smaller than we are presently estimating; 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 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 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 Verastem Oncology 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/20231014680900/en/
Investors: Dan Calkins Investor Relations +1 781-469-1694
dcalkins@verastem.com
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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