Previous Data from Investigator-Initiated Phase
1/2 Trial Show Encouraging Response Rates, Durability and a
Favorable Safety Profile
Phase 2 Adaptive Trial Design to Evaluate
VS-6766 Alone and in Combination with Defactinib
Verastem to Seek FDA Accelerated Approval,
Pending Trial Outcome
Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology),
a biopharmaceutical company committed to advancing new medicines
for patients battling cancer, today announced the initiation of a
Phase 2 registration-directed clinical trial of VS-6766, its
RAF/MEK inhibitor, and defactinib, its FAK inhibitor, in patients
with recurrent low-grade serous ovarian cancer (LGSOC).
“Results to date have demonstrated the clinical activity of
VS-6766 and defactinib in KRAS mutant cancers, signaling
potentially promising clinical results in low-grade serous ovarian
cancer and in KRAS-G12V mutant non-small cell lung cancer,” said
Brian Stuglik, Chief Executive Officer of Verastem Oncology. “The
start of our registration-directed trial in recurrent LGSOC is a
significant milestone in our work to develop the backbone of
therapy for RAS driven tumors, an area of minimal therapeutic
results, significant toxicity and limited treatment options.”
The Phase 2 study (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.1 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. Trial enrollment is
underway in the United States with European sites to follow.
Additional information about this study can be found here on
ClinicalTrials.gov (NCT04625270). The Company previously announced
its successful meeting with the Food and Drug Administration (FDA)
in Q3 2020 and the FDA’s support of the Company’s development
strategy and adaptive trial design for LGSOC.
According to Susana Banerjee, M.D., Ph.D., Medical Oncologist
and Research Lead for the Gynaecology Unit at The Royal Marsden and
Team Leader at The Institute of Cancer Research, London, Global and
Lead European Investigator of this trial, “Based on my experience
treating patients with low-grade serous ovarian cancer in the Phase
1/2 FRAME trial, I have seen firsthand the potential for the
combination of VS-6766 and defactinib, particularly in KRAS mutated
tumors, which may address the significant limitations we have seen
with other therapeutic approaches. This trial will further explore
the encouraging response rates, durability and safety profile of
VS-6766 and defactinib demonstrated in early phase studies and
enable us to evaluate VS-6766 alone and in combination with
defactinib to address the unmet needs of women with this specific
type of ovarian cancer.”
“LGSOC is a difficult to treat disease most often diagnosed in
women between the ages of 45 to 55 years.2 The majority of these
patients experience a significant amount of pain and impact on
their lives over a long period of time as response rates with
current therapies have historically been low and the toxicity
profiles of these agents make it difficult to keep patients on
therapy,” said Rachel N. Grisham, M.D., Section Head, Ovarian
Cancer and Director, Gynecologic Medical Oncology at Memorial Sloan
Kettering Cancer Center in Westchester, NY and the study’s
principal US investigator. “This trial represents an opportunity to
further evaluate the potential for improved outcomes for patients
with LGSOC.”
The launch of the trial follows the recent results of two
clinical trials led by Professor Udai Banerji, Deputy Director of
Drug Development at The Institute of Cancer Research, London, and
The Royal Marsden NHS Foundation Trust. The first, a Phase 1 trial
published in The Lancet Oncology, showed that VS-6766 could be
effective against a range of KRAS-mutated tumor types, including
lung and gynecological cancers.3 The second, a Phase 1/2 trial
presented at the American Association for Cancer Research (AACR)
Annual Meeting 2020, showed the combination of a RAF/MEK and FAK
inhibitor could be beneficial for patients with KRAS mutant
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.2 It
comprises 5-10% of serous ovarian cancers and 6-8% of all ovarian
cancers.2 There are an estimated 6,000 patients in the U.S. and
80,000 worldwide living with this disease.5 LGSOC is most often
diagnosed in women between the ages of 45-55 years.2 LGSOC has a
median survival of approximately 10 years,2 with 85% of patients
experiencing recurrence6 and enduring severe pain and complications
as the disease progresses. Chemotherapy is the standard of care for
this disease.2
About VS-6766
VS-6766 is an oral small molecule inhibitor of the RAF/MEK
signaling pathway. In contrast to other MEK inhibitors in
development, VS-6766 blocks both MEK kinase activity and the
ability of RAF to phosphorylate MEK. This unique mechanism allows
VS-6766 to block MEK signaling without the compensatory activation
of MEK that appears to limit the efficacy of other inhibitors.
About Defactinib
Defactinib (VS-6063) is an oral small molecule inhibitor of FAK
and PYK2 that is currently being evaluated as a potential
combination therapy for various solid tumors. The Company has
received Orphan Drug designation for defactinib in ovarian cancer
in the US, EU and Australia. Preclinical research by Verastem
Oncology scientists and collaborators at world-renowned research
institutions has described the effect of FAK inhibition to enhance
immune response by decreasing immuno-suppressive cells, increasing
cytotoxic T cells, and reducing stromal density, which allows
tumor-killing immune cells to enter the tumor.7,8
About the VS-6766/Defactinib Combination
RAS mutant tumors are present in ~30% of all human cancers, have
historically presented a difficult treatment challenge and are
often associated with significantly worse prognosis.9 Challenges
associated with identifying new treatment options for these types
of cancers include resistance to single agents, 10 identifying
tolerable combination regimens with MEK inhibitors and new RAS
inhibitors in development addressing only a minority of all RAS
mutated cancers.
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.
Updated data from this study presented at the 2nd Annual
RAS-Targeted Drug Development Summit in September 2020 demonstrated
a 56% overall response rate and long duration of therapy among
patients with KRAS-G12 mt LGSOC.10 Based on an observation of
higher response rates seen in NSCLC patients with KRAS-G12V
mutations in the study, Verastem will also be further exploring the
role of VS-6766 and defactinib in KRAS-G12V NSCLC. The FRAME study
was expanded in August 2020 to include new cohorts in pancreatic
cancer, KRAS mutant endometrial cancer and KRAS-G12V NSCLC.
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 and the timing of commencing a
registration-directed trial 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 make additional draws under our debt facility or
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-Q
for the period ended September 30, 2020 as filed with the
Securities and Exchange Commission (SEC) on November 9, 2020 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.
References
_______________________________________
1 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?term=vs-6766&draw=2&rank=1.
Accessed November 24, 2020.
2 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 November 24, 2020.
3 Verastem Press Release. Verastem
Oncology Announces New Data Published in The Lancet Oncology
Supports Potential of VS-6766 as Treatment for RAS Mutant Tumors.
October 28, 2020. Available at:
https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-new-data-published-lancet-oncology.
Accessed November 24, 2020.
4 Verastem Press Release. Verastem
Oncology Announces Preliminary Data from Investigator-initiated
Study Highlighting Clinical Activity of RAF/MEK and FAK Combination
in KRAS Mutant Tumors Presented at the American Association for
Cancer Research 2020 Virtual Annual Meeting. April 27, 2020.
Available at:
https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-preliminary-data-investigator.
Accessed November 24, 2020.
5 Slomovitz, Gourley, Carey, Malpica,
Shih, Huntsman, Fader., Grisham et al, Low-Grade serous ovarian
cancer: State of the Science; Gynecol Oncol; 2020.
6 Corrado G, Salutari V, Palluzzi E,
Distefano MG, Scambia G, Ferrandina G. Optimizing treatment in
recurrent epithelial ovarian cancer. Expert Rev Anticancer Ther.
2017;17:1147-1158. doi: 10.1080/14737140.2017.1398088
7 Chénard-Poirier, M. et al. Results from
the biomarker-driven basket trial of RO5126766 (CH5127566), a
potent RAF/MEK inhibitor, in RAS- or RAF-mutated malignancies
including multiple myeloma. Journal of Clinical Oncology 2017: 35.
10.1200/JCO.2017.35.15_suppl.2506.
8 ClinicalTrials.gov. Phase I Trial of
VS-6063 and RO5126766. (FRAME). Available at:
https://clinicaltrials.gov/ct2/show/NCT03875820. Accessed November
24, 2020.
9 Baines, A. T., Xu, D., & Der, C. J.
(2011). Inhibition of Ras for cancer treatment: the search
continues. Future medicinal chemistry, 3(14), 1787–1808.
https://doi.org/10.4155/fmc.11.121
10 Verastem Press Release. Verastem
Oncology Announces Presentation of Updated Phase 1/2 FRAME Study
Data at the 2nd Annual RAS-Targeted Drug Development Summit.
September 16, 2020. Available at:
https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-presentation-updated-phase-12-frame.
Accessed November 24, 2020.
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version on businesswire.com: https://www.businesswire.com/news/home/20201130005327/en/
Investors: John Doyle Vice President, Investor Relations &
Finance +1 781-469-1546 jdoyle@verastem.com
Media: Lisa Buffington Corporate Communications +1 781-292-4205
lbuffington@verastem.com
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