Phase 1/2 Study Expected to Enroll
Approximately 100 Patients at up to 15 sites in the U.S.
Verastem, Inc., (NASDAQ:VSTM) today announced dosing of the
first patient in a new clinical trial evaluating avelumab*, an
investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in
combination with Verastem’s defactinib**, an investigational focal
adhesion kinase (FAK) inhibitor, in patients with advanced ovarian
cancer. The Phase 1/2 clinical trial is being conducted in
collaboration with the alliance between Merck KGaA, Darmstadt,
Germany, which in the US and Canada operates as EMD Serono, and
Pfizer, and is expected to enroll approximately 100 patients at up
to 15 sites across the U.S.
Robert Forrester, President and Chief Exececutive Officer of
Verastem, stated, “Initiation of this clinical trial evaluating the
combination of avelumab and defactinib represents an important
milestone for Verastem, and together with our collaborators at
Merck KGaA, Darmstadt, Germany, and Pfizer, we are eager to
evaluate the potential of this combination to provide ovarian
cancer patients with a new treatment option.”
The Phase 1/2 multicenter, open-label, dose-escalation and dose
expansion study is designed to assess the safety, pharmacokinetics,
pharmacodynamics, and initial observations of clinical activity of
the avelumab/defactinib combination in patients with recurrent or
refractory stage III-IV ovarian cancer. Additional primary
objectives of the study include identification of the recommended
Phase 2 dose (RP2D), and assessment of the best overall response
according to Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1.
“Our goal, through this collaboration, is to increase our
understanding of FAK inhibition, and further demonstrate the
alliance’s commitment to exploring a diverse range of novel
combinations with avelumab,” said Chris Boshoff, M.D., Ph.D.,
Senior Vice President and Head of Immuno-oncology, Early
Development and Translational Oncology, Pfizer Global Product
Development.
“Patients with late-stage ovarian cancer are in dire need of
effective new treatments. We are eager to review the results of
this important study as we continue to investigate the potential of
avelumab to address the unmet needs for this hard-to-treat cancer,”
said Dr. Alise Reicin, Head of Global Clinical Development at Merck
KGaA, Darmstadt, Germany’s biopharma business.
FAK is a protein which is often overproduced in tumors, enabling
cancer cells to evade attack by the immune system. As reported in
Cell, and Nature Medicine, pre-clinical research shows that FAK
inhibition can modulate the balance of immune cells in the tumor,
increasing the presence of cytotoxic T cells in the tumor and
decreasing the presence of immunosuppressive T regulatory
cells.1,2
*Avelumab is under clinical investigation and has not been
proven to be safe and effective. There is no guarantee any product
will be approved in the sought-after indication by any health
authority worldwide.
**VS-6063 (defactinib) is under clinical investigation and has
not be proven to be safe and effective. There is no guarantee any
product will be approved in the sought-after indication by any
health authority worldwide.
More About the Phase 1/2 Study
The study is comprised of 2 sequential parts: Part A (Dose
Escalation) and Part B (Expansion). In Part A (Dose Escalation),
approximately 18 subjects will receive avelumab IV treatment in
28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15)
and oral defactinib twice-daily (BID) continuously starting on Day
1 of Cycle 1. Subject enrollment will proceed according to a
standard 3+3 design. In the absence of dose-limiting toxicity, each
subject will receive the study drug regimen for a minimum of 28
days (Cycle 1) and may continue to receive additional cycles of
study treatment until disease progression has been documented or
unacceptable toxicity or other treatment discontinuation criteria
have been met. All subjects in a cohort must have completed at
least 1 cycle of dosing before dose escalation involving new
subjects entered into the next dose cohort can occur. Based on the
safety and PK data obtained in the dose escalation portion of the
study, the RP2D of the combination will be determined.
In Part B (Expansion), approximately 80 subjects will be
enrolled and will receive avelumab IV treatment in 28-day cycles
(10 mg/kg over approximately 1 hour on Days 1 and 15) and oral
defactinib at the RP2D dose continuously starting on Day 1 of Cycle
1.
Additional information on the clinical trial can be found at:
http://bit.ly/2g6bnXA
About Ovarian Cancer
Globally, ovarian cancer is the seventh most common cancer in
women.3 Annually, nearly 239,000 cases are diagnosed worldwide.4
Ovarian cancer may be difficult to diagnose, as symptoms may appear
only in the later stages, when the disease has spread beyond the
ovaries.4 Outcomes for women with ovarian cancer are generally poor
due to most patients presenting with advanced disease.5 The 5-year
prevalence of women globally living with ovarian cancer is 22.6 per
100,000.4 Current treatment options for epithelial ovarian cancer
may include surgery, radiotherapy, chemotherapy and targeted
therapies.6 Women who are unable to undergo treatment with
platinum-based chemotherapy, due to resistance or refractory
disease, currently have very limited treatment options.
Platinum-resistant ovarian cancer is defined as ovarian cancer that
recurs within six months of completing primary chemotherapy with a
platinum-based medication.7 Platinum-refractory ovarian cancer is
defined as ovarian cancer that progresses during treatment with a
platinum-based chemotherapy regimen.7 There is still a clear unmet
need in ovarian cancer in relation to general disease awareness,4
improving initial investigations in primary and secondary care and
novel therapies with demonstrable efficacy.8
About Avelumab
Avelumab (also known as MSB0010718C) is an investigational fully
human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1
interactions, avelumab is thought to enable the activation of
T-cells and the adaptive immune system. By retaining a native
Fc-region, avelumab is thought to potentially engage the innate
immune system and induce antibody-dependent cell-mediated
cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt,
Germany, and Pfizer announced a strategic alliance to co-develop
and co-commercialize avelumab.
About Defactinib
Defactinib (VS-6063) is an investigational inhibitor of Focal
Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by
the PTK-2 gene that mediates oncogenic signaling in response to
cellular adhesion and growth factors.9 Based on the multi-faceted
roles of FAK, defactinib is used to treat cancer through modulation
of the tumor microenvironment, enhancement of anti-tumor immunity,
and reduction of cancer stem cells.1,2 Defactinib is currently
being evaluated in three separate clinical collaborations in
combination with immunotherapeutic agents for the treatment of
several different cancer types including pancreatic, ovarian,
non-small cell lung cancer, and mesothelioma. These studies are
combination clinical trials with pembrolizumab and avelumab from
Merck & Co. and Pfizer/Merck KGaA, Darmstadt, Germany,
respectively.11,12,13 Information about these and additional
clinical trials evaluating the safety and efficacy of defactinib
can be found on www.clinicaltrials.gov.
About Verastem, Inc.
Verastem, Inc. (NASDAQ:VSTM) is a biopharmaceutical company
focused on discovering and developing drugs to improve outcomes for
patients with cancer. Verastem is currently developing duvelisib, a
dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and
PI3K-gamma, which has successfully met its primary endpoint in a
Phase 2 study and is currently being evaluated in a Phase 3
clinical trial in patients with chronic lymphocytic leukemia (CLL).
Other clinical product candidates include focal adhesion kinase
(FAK) inhibitors defactinib and VS-4718, and dual PI3K/mTOR
inhibitor VS-5584. Defactinib is currently being evaluated in three
separate clinical collaborations in combination with
immunotherapeutic agents for the treatment of several different
cancer types, including pancreatic, ovarian and non-small cell lung
cancer, and mesothelioma. Verastem’s product candidates seek to
treat cancer by modulating the local tumor microenvironment,
enhancing anti-tumor immunity and reducing cancer stem cells. For
more information, please visit www.verastem.com.
Alliance between Merck KGaA, Darmstadt Germany, and Pfizer
Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt,
Germany,and Pfizer Inc. The global strategic alliance between Merck
KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables
the companies to benefit from each other’s strengths and
capabilities and further explore the therapeutic potential of
avelumab, an investigational anti-PD-L1 antibody initially
discovered and developed by Merck KGaA, Darmstadt, Germany. The
immuno-oncology alliance will jointly develop and commercialize
avelumab and advance Pfizer’s PD-1 antibody. The alliance is
focused on developing high-priority international clinical programs
to investigate avelumab, as a monotherapy, as well as combination
regimens, and is striving to find new ways to treat cancer.
Verastem forward-looking statements notice
This press release includes forward-looking statements about
Verastem’s strategy, future plans and prospects, including
statements regarding the development and activity of VS-6063
(defactinib), Verastem’s FAK and diagnostics programs generally,
the structure of our planned and pending clinical trials and the
timeline for clinical development, our rights to develop or
commercialize our product candidates and our ability to finance
contemplated development activities and fund operations for a
specified period. The words “anticipate,” “appear,” “believe,”
“estimate,” “expect,” “intend,” “may,” “plan,” “predict,”
“project,” “target,” “potential,” “will,” “would,” “could,”
“should,” “continue,” 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 that the preclinical testing of
Verastem’s product candidates and preliminary or interim data from
clinical trials may not be predictive of the results or success of
ongoing or later clinical trials, that data may not be available
when we expect it to be, that enrollment of clinical trials may
take longer than expected, that our product candidates will cause
unexpected safety events, that Verastem will be unable to
successfully initiate or complete the clinical development of its
product candidates, that the development of Verastem’s product
candidates will take longer or cost more than planned, and that
Verastem’s product candidates will not receive regulatory approval
or become commercially successful products. Other risks and
uncertainties include those identified under the heading “Risk
Factors” in Verastem’s Annual Report on Form 10-K for the year
ended December 31, 2015 as filed on March 3, 2016, Verastem's
quarterly report on Form 10-Q filed on November 7, 2016 and in any
subsequent SEC filings. The forward-looking statements contained in
this press release reflect Verastem’s current views with respect to
future events, and Verastem does not undertake and specifically
disclaims any obligation to update any forward-looking
statements.
References
1. Serrels A et al. FAK Controls Chemokine Transcription, Tregs,
and Evasion of Anti-tumor Immunity. Cell 2015; 163 (1): 160–73
2. Jiang H et al. Targeting focal adhesion kinase renders
pancreatic cancers responsive to checkpoint immunotherapy. Nat Med
2016: Aug 22(8) 851-60.
3. Ferlay J et al. GLOBOCAN 2012 v1.0, Cancer Incidence and
Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon,
France: International Agency for Research on Cancer; 2013.
Available from: http://globocan.iarc.fr. Accessed December
2015.
4. World Cancer Research Fund International. Ovarian Cancer
Statistics. Available from:
http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/ovarian-cancer-statistics.
Accessed November 2015.
5. NICE. Ovarian Cancer: Recognition and Initial Management.
Available from: https://www.nice.org.uk/guidance/cg122. Accessed
November 2015.
6. National Cancer Institute. Ovarian Epithelial, Fallopian
Tube, and Primary Peritoneal Cancer Treatment (PDQ®). Available
from:http://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq
Accessed November 2015.
7. Ledermann JA et al. Newly diagnosed and relapsed epithelial
ovarian carcinoma: ESMO clinical practice guidelines for diagnosis,
treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi24–32.
8. Ojalvo LS et al. Emerging immunotherapies in ovarian cancer.
Discov Med 2015; 20(109): 97–109.
9. Schaller MD and Parsons JT. Focal adhesion kinase: an
integrin-linked protein tyrosine kinase. Trends Cell Biol. 1993 3:
258-62.
10. Sulzmaier FJ et al. FAK in cancer: mechanistic findings and
clinical applications. Nature Rev Cancer. 2014 14: 598-610.
11. www.clinicaltrials.gov, NCT02546531
12. www.clinicaltrials.gov, NCT02943317
13. www.clinicaltrials.gov, NCT02758587
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VerastemMedia and Investor Relations:Brian Sullivan, +1
781 292 4214
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