WALTHAM, Mass.--(BUSINESS WIRE)--Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, today announced that it has initiated an open-label, multicenter, Phase 1b/2 study of rebastinib, the Company’s investigational small molecule switch control inhibitor of TIE2 kinase, in combination with carboplatin in patients with advanced or metastatic solid tumors.
“We are extremely pleased with the recent progress made on our rebastinib program, including today’s announcement that we have initiated a second Phase 1b/2 clinical study of rebastinib in combination with chemotherapy,” said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. “This second clinical study will evaluate rebastinib in combination with carboplatin, a treatment regimen that, based on preclinical observations, we believe has the potential to be an important new approach to treating patients with advanced solid tumors.”
Part 1 (3+3 dose escalation) of this two part study is designed to evaluate the safety, tolerability and pharmacokinetics of 50 mg and 100 mg rebastinib twice daily (BID) when administered in combination with carboplatin, and to determine the recommended phase 2 dose (RP2D) of rebastinib in combination with carboplatin, in patients with advanced or metastatic solid tumors that are refractory to standard therapies. In part 2, the safety, tolerability and efficacy of the RP2D of rebastinib in combination with carboplatin administered once every 3 weeks will be assessed across multiple disease cohorts, including: breast cancer, ovarian cancer, and mesothelioma. This trial is expected to enroll up to 117 patients in total, with approximately 18 patients in part 1 and up to 99 patients in part 2. For more information about the clinical trial design please visit www.clinicaltrials.gov (NCT03717415).
“The biological mechanisms by which tumors co-opt the surrounding microenvironment to grow, survive and become more invasive, are becoming better understood. Recent research indicates that TIE2 kinase is involved in multiple mechanisms favoring a pro-tumoral microenvironment, including the regulation of a population of immunosuppressive macrophages, promotion of tumor angiogenesis, and function of perivascular pumps that lead to tumor cell recruitment and metastasis,” said Daniel L. Flynn, Ph.D., Chief Scientific Officer of Deciphera. “In addition, use of chemotherapeutic agents are believed to enhance the recruitment of these macrophages, leading to increased tumor vascularization and dissemination. In preclinical studies rebastinib has been shown to block these unintended effects of chemotherapy, providing rationale for the potential combination of rebastinib with chemotherapy.”
Preclinical information on the role of TIE2 kinase was published in
Molecular Cancer Therapeutics, 2017; 16: 2486-2501 and Science
Translational Medicine, July 5, 2017; 9: eaan0026.
(www.deciphera.com/science/presentation-publications/)
About Rebastinib
Rebastinib is an investigational, orally
administered, potent and selective inhibitor of the TIE2 kinase, the
receptor for angiopoietins, an important family of vascular growth
factors in the tumor microenvironment that also activate pro-tumoral
TIE2 expressing macrophages. In a Phase 1 clinical study, biomarker data
have demonstrated rebastinib-induced increases in the TIE2 ligand
angiopoietin 2, secondary to TIE2 inhibition. Rebastinib is currently
being evaluated in a Phase 1b/2 clinical study in combination with
paclitaxel (NCT03601897), in a Phase 1b/2 clinical study in combination
with carboplatin (NCT03717415), and in an investigator sponsored Phase
1b trial in patients with metastatic breast cancer in combination with
paclitaxel or eribulin (NCT02824575).
About Deciphera Pharmaceuticals
Deciphera Pharmaceuticals is
a clinical-stage biopharmaceutical company focused on improving the
lives of cancer patients by tackling key mechanisms of drug resistance
that limit the rate and/or durability of response to existing cancer
therapies. Our small molecule drug candidates are directed against an
important family of enzymes called kinases, known to be directly
involved in the growth and spread of many cancers. We use our deep
understanding of kinase biology together with a proprietary chemistry
library to purposefully design compounds that maintain kinases in a
“switched off” or inactivated conformation. These investigational
therapies comprise tumor-targeted agents designed to address therapeutic
resistance causing mutations and immuno-targeted agents designed to
control the activation of immunokinases that suppress critical immune
system regulators, such as macrophages. We have used our platform to
develop a diverse pipeline of tumor-targeted and immuno-targeted drug
candidates designed to improve outcomes for patients with cancer by
improving the quality, rate and/or durability of their responses to
treatment.
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Cautionary Note Regarding Forward-Looking Statements
This
press release contains forward-looking statements within the meaning of
the Private Securities Litigation Reform Act of 1995, as amended,
including, without limitation, statements regarding our expectations of
our clinical trials with our investigational agent rebastinib,
including, without limitation, our study of rebastinib in combination
with carboplatin, and the potential for rebastinib, alone or in
combination with other agents or chemotherapy to treat cancers. The
words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,”
“anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,”
“potential,” “continue,” “target” and similar expressions are intended
to identify forward-looking statements, although not all forward-looking
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expectations and beliefs and are subject to a number of risks,
uncertainties and important factors that may cause actual events or
results to differ materially from those expressed or implied by any
forward-looking statements contained in this press release, including,
without limitation, risks and uncertainties related to the delay of any
current or planned clinical studies or the development of our drug
candidates, including ripretinib (DCC-2618), rebastinib, and DCC-3014,
our advancement of multiple early-stage and later-stage efforts, our
ability to successfully demonstrate the efficacy and safety of our drug
candidates including in later-stage studies, the preclinical and
clinical results for our drug candidates, which may not support further
development of such drug candidates, our efforts to scale up drug
product manufacturing, our ability to implement commercial readiness,
actions of regulatory agencies, any or all of which may affect the
initiation, timing and progress of clinical studies and other risks
identified in our SEC filings, including our Quarterly Report on Form
10-Q for the quarter ended September 30, 2018, and subsequent filings
with the SEC. We caution you not to place undue reliance on any
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of the date hereof and should not be relied upon as representing its
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to update any forward-looking statements.
