Results of Early Trial Demonstrate 70% Overall
Response Rate (ORR) in Patients with KRAS Mutant Tumors, 44% ORR in
KRAS Wild-Type Tumors and 52% ORR in All Evaluable Patients with a
Favorable Safety Profile
Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology),
a biopharmaceutical company committed to advancing new medicines
for patients battling cancer, today announced that the U.S. Food
and Drug Administration (FDA) granted Breakthrough Therapy
designation for the combination of its investigational RAF/MEK
inhibitor VS-6766, 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.
“Patients with low-grade serous ovarian cancer urgently need
better solutions due to low response rates and tolerability issues
associated with current therapies,” said Melissa Aucoin, CEO of the
National Ovarian Cancer Coalition. “A Breakthrough Therapy
designation in this disease is a significant step forward for the
women who often, at a relatively young age, start a lengthy battle
with this highly recurrent and impactful disease.”
The combination of VS-6766 with defactinib is being evaluated in
the ongoing investigator-initiated Phase 1/2 FRAME trial. In the
most recent read-out from the FRAME LGSOC cohort (n=24), the
overall response rate (ORR) is 52% (11 of 21 response evaluable
patients), with KRAS mutant ORR at 70% (7 of 10 response evaluable
patients), KRAS wild-type ORR at 44% (4 of 9 response evaluable
patients) and KRAS status undetermined ORR at 0% (0 of 2 response
evaluable patients). The most common side effects seen in the study
were rash, creatine kinase elevation, nausea, hyperbilirubinemia
and diarrhea, most being NCI CTC Grade 1/2 and all were reversible.
Several patients have been on therapy for more than one year,
indicating the potential for a long duration of benefit.
“Breakthrough Therapy designation will facilitate our efforts to
verify the robust and durable response and compelling safety
profile of VS-6766 with defactinib that we have seen in patients
with LGSOC and potentially bring a new therapy to these patients as
quickly as possible,” said Brian Stuglik, CEO of Verastem Oncology.
“The majority of LGSOC is RAS pathway-driven, and we are committed
to exploring the potential for VS-6766 as a backbone therapy across
RAS pathway-driven solid tumors.”
RAS is the most frequently mutated oncogene, occurring in 30% of
human cancers.1,2 These cancers are typically highly aggressive and
recurrent, sending signaling commands through the RAS pathway.
VS-6766 is a novel dual inhibitor of the RAF/MEK signaling pathway.
With this unique dual mechanism of action, VS-6766 confers vertical
inhibition of the RAS pathway in a single drug. Verastem Oncology
is evaluating VS-6766 in combination with agents targeting other
nodes in the RAS pathway as well as with agents targeting parallel
pathways to address multiple cancer indications and mutations.
Breakthrough Therapy designation allows for the expedited
development and review of drugs for serious or life-threatening
conditions. The designation requires preliminary clinical evidence
that demonstrates the drug or combination may have substantial
improvement on at least one clinically relevant endpoint over
available therapy.3
Verastem Oncology is currently evaluating the combination of
VS-6766 alone and with defactinib in a Phase 2
registration-directed trial. RAMP 201 (Raf And
Mek Program) (ENGOTov60/GOG3052) is an adaptive
two-part multicenter, parallel cohort, randomized, open label trial
to evaluate the efficacy and safety of VS-6766 alone and in
combination with defactinib in patients with recurrent LGSOC.4
About Low Grade Serous Ovarian Cancer (LGSOC)
Low-grade serous ovarian cancer (LGSOC) is a recurrent,
chemotherapy-resistant cancer with a high mortality rate.5 It
comprises 5-10% of serous ovarian cancers and 6-8% of all ovarian
cancers.6 There are an estimated 6,000 patients in the U.S. and
80,000 worldwide living with this disease.6 LGSOC is most often
diagnosed in women between the ages of 45-55 years.6 LGSOC has a
median survival of approximately 10 years,6 with 85% of patients
experiencing recurrence7 and enduring severe pain and complications
as the disease progresses. Chemotherapy is the standard of care for
this disease.6
About the VS-6766/Defactinib Combination
The combination of VS-6766 and defactinib has been found to be
clinically active in patients with KRAS mutant tumors. In an
ongoing investigator-initiated Phase 1/2 FRAME study, the
combination of VS-6766 and defactinib is being evaluated in
patients with LGSOC, KRAS mutant NSCLC and colorectal cancer (CRC).
The FRAME study was expanded to include new cohorts in pancreatic
cancer, KRAS mutant endometrioid cancer and KRAS-G12V NSCLC.
Verastem Oncology is also supporting an investigator-initiated
Phase 2 trial evaluating VS-6766 with defactinib in patients with
metastatic uveal melanoma.
Verastem Oncology has initiated Phase 2 registration-directed
trials of VS-6766 with defactinib in patients with recurrent LGSOC
and in patients with recurrent KRAS-G12V mutant NSCLC as part of
its RAMP (Raf And Mek Program).
About RAMP
Verastem Oncology has initiated Phase 2 registration-directed
trials evaluating the combination of VS-6766 alone and with
defactinib in patients with recurrent LGSOC and in patients with
recurrent KRAS-G12V mutant NSCLC as part of its RAMP (Raf
And Mek Program).
RAMP 201 (ENGOTov60/GOG3052) is an adaptive, two-part
multicenter, parallel cohort, randomized, open-label trial to
evaluate the efficacy and safety of VS-6766 alone and in
combination with defactinib in patients with recurrent LGSOC.8 The
first part of the study will determine the optimal regimen of
either VS-6766 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.
RAMP 202 is an adaptive, two-part multicenter, parallel cohort,
randomized, open-label trial to evaluate the efficacy and safety of
VS-6766 alone and in combination with defactinib in patients with
KRAS mutant NSCLC, following treatment with a platinum-based
regimen and immune checkpoint inhibitor.9 The first part of the
study will determine the optimal regimen of either VS-6766
monotherapy or in combination with defactinib in patients with
KRAS-G12V mutant NSCLC randomized 1:1 in each treatment arm. An
exploratory arm of the initial phase of the study will evaluate
other KRAS mutations. The determination of which regimen to take
forward into the expansion phase of the trial will be made based on
data from KRAS-G12V mutant patients. The second phase of the study
will examine efficacy and safety parameters of the most effective
regimen.
For more information, please visit www.RAMP201Study.com and
www.RAMP202Study.com.
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 the
RAF/MEK/FAK combination, the potential benefits of Breakthrough
Therapy designation and the timing of commencing and completing
registration-directed trials for the RAF/MEK/FAK combination. 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 defactinib in combination with VS-6766; 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 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 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; that we or Chugai Pharmaceutical Co., Ltd. will fail to
fully perform under the VS-6766 license agreement; 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 we will be unable to
execute on our partnering strategies for defactinib in combination
with VS-6766; 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, 2020 as filed with the Securities
and Exchange Commission (SEC) on March 18, 2021 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.
1 Timar J, Kashofer K. Molecular epidemiology and diagnostics of
KRAS mutations in human cancer. Cancer and Metastasis Reviews.
2020;39:1029–1038. https://doi.org/10.1007/s10555-020-09915-5. 2
Baines T. A, Xu D, Der C. J. Inhibition of Ras for cancer
treatment: the search continues. Future Medicinal Chemistry.
2011;3(14):1787–1808. https://doi.org/10.4155/fmc.11.121. 3 U.S.
Food and Drug Administration. Breakthrough Therapy.
https://www.fda.gov/forpatients/approvals/fast/ucm405397.htm 4
Clinicaltrials.gov. A Study of VS-6766 v. VS-6766 + Defactinib in
Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS
Mutation. Available at:
https://clinicaltrials.gov/ct2/show/NCT04625270?cond=vs6766&draw=2&rank=1.
Accessed April 9, 2021. 5 Grisham R. Low grade serous carcinoma of
the ovary. Oncology. 2016; 30(7):650-652. Available at:
https://www.cancernetwork.com/view/low-grade-serous-carcinoma-ovary.
Accessed April 9, 2021. 6 Slomovitz B, Gourley C, Carey S. M,
Malpica A, Shih I, Huntsman D, et al. Low-Grade serous ovarian
cancer: State of the Science. Gynecol Oncol. 2020;156(3):715-725.
https://doi.org/10.1016/j.ygyno.2019.12.033. 7 Corrado G, Salutari
V, Palluzzi E, Distefano MG, Scambia G, Ferrandina G. Optimizing
treatment in recurrent epithelial ovarian cancer. Expert Rev
Anticancer Ther. 2017;17(12):1147-1158.
https://doi.org/10.1080/14737140.2017.1398088 8 Clinicaltrials.gov.
A Study of VS-6766 v. VS-6766 + Defactinib in Recurrent Low-Grade
Serous Ovarian Cancer With and Without a KRAS Mutation. Available
at:
https://clinicaltrials.gov/ct2/show/NCT04625270?cond=vs6766&draw=2&rank=1.
Accessed April 9, 2021. 9 Clinicaltrials.gov. A Study of VS-6766 v.
VS-6766 + Defactinib in Recurrent G12V or Other KRAS-Mutant
Non-Small Cell Lung Cancer. Available at:
https://clinicaltrials.gov/ct2/show/NCT04620330?term=VS-6766&draw=2&rank=2.
Accessed April 9, 2021.
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version on businesswire.com: https://www.businesswire.com/news/home/20210524005362/en/
Investors: Ajay Munshi Vice President, Corporate
Development +1 781-469-1579 amunshi@verastem.com
Sherri Spear Argot Partners +1 212 600 1902
sherri@argotpartners.com
Media: Lisa Buffington Corporate Communications +1
781-292-4205 lbuffington@verastem.com
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