Deciphera Pharmaceuticals Presents Data from Rebastinib & DCC-3116 Programs at the AACR-NCI-EORTC International Conference on...
October 28 2019 - 12:30PM
Business Wire
- Combination of Rebastinib and Paclitaxel
Exhibited Encouraging Preliminary Anti-tumor Activity Across
Treatment Arms in the Ongoing Phase 1b/2 Clinical Study -
- DCC-3116 Represents a Differentiated Approach
to Autophagy Inhibition and a First-in-Class Opportunity for a New
Therapeutic Modality in Mutant RAS Cancers -
Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage
biopharmaceutical company addressing key mechanisms of tumor drug
resistance, today presented data from its ongoing Phase 1b/2
clinical study of rebastinib, an oral TIE2 kinase inhibitor, in
combination with paclitaxel at the AACR-NCI-EORTC International
Conference on Molecular Targets and Cancer Therapeutics in Boston.
In addition, the Company also presented data from preclinical
studies of DCC-3116, a potential first-in-class autophagy inhibitor
to treat mutant RAS cancers.
“Both of these datasets highlight the broad applicability of
Deciphera’s kinase switch control platform and our potential to
address unmet needs in oncology,” said Matthew L. Sherman, M.D.,
Executive Vice President and Chief Medical Officer of Deciphera.
“We look forward to continuing Part 2 of our Phase 1b/2 study of
rebastinib in combination with paclitaxel with the insights
garnered from Part 1 of the study. We also look forward to
advancing the IND-enabling studies for DCC-3116.”
Rebastinib
The Phase 1b/2 study of rebastinib in combination with
paclitaxel is a two-part, open-label, multicenter study assessing
the safety, tolerability, anti-tumor activity and pharmacokinetics
of multiple doses of rebastinib in patients with advanced or
metastatic solid tumors. Data presented today are from 43 patients
from Part 1 of the study, including 24 patients from the rebastinib
50 mg oral twice a day (BID) with paclitaxel 80 mg/m2 IV cohort and
19 patients from the rebastinib 100 mg oral BID with paclitaxel 80
mg/m2 IV cohort. Preliminary results from Part 1 included:
- Encouraging preliminary anti-tumor activity was observed in
both dose cohorts, with objective responses seen across a heavily
pre-treated patient population, including patients with prior
exposure to paclitaxel. Objective responses were seen in eight
patients including ovarian (3), breast (2), carcinosarcoma (2), and
peritoneal mesothelioma (1), seven of whom had prior therapy with
paclitaxel or docetaxel. A best response of partial response (PR)
was observed in 5 of 24 patients in the 50 mg BID dose cohort and 3
of 19 patients in the 100 mg BID dose.
- Exposure to rebastinib was dose-proportional at the 50 mg BID
and 100 mg BID doses when given in combination with
paclitaxel.
- Mean circulating Ang-2 levels increased with exposure to higher
doses of rebastinib in combination with paclitaxel, indicating TIE2
inhibition.
- Rebastinib in combination with paclitaxel was generally
well-tolerated, with similar frequency of treatment-emergent
adverse events (TEAEs) between the two dose cohorts, and most TEAEs
were consistent with first-in-human studies of rebastinib or known
to be associated with treatment with paclitaxel.
- Based on the observed frequency of muscular weakness in
preliminary data from the ongoing Part 2 portion of the study with
the 100 mg BID dose, the recommended phase 2 dose (RP2D) was
changed to 50 mg BID.
DCC-3116
DCC-3116 is designed as a potential autophagy inhibitor by
selectively targeting ULK kinase. Autophagy is a cellular pathway
that has been shown to be upregulated in mutant RAS cancers and
that also mediates resistance to inhibitors of the RAS signaling
pathway. Subject to favorable investigational new drug
(IND)-enabling studies and filing and activation of an IND
application, Deciphera intends to develop DCC-3116 for the
potential treatment of mutant RAS cancers in combination with
inhibitors of downstream effector targets including RAF, MEK, or
ERK inhibitors (MAPK inhibitors) as well as with direct inhibitors
of mutant RAS. Preclinical data presented today included the
following:
- DCC-3116 was shown to be a potent, selective, and tight-binding
inhibitor of ULK kinase.
- DCC-3116 inhibited phosphorylation of the ULK substrate ATG13
in cancer cells and exhibited synergy in vitro in combination with
MAPK inhibitors in inhibiting cancer cell growth.
- Oral doses of DCC-3116 led to sustained inhibition of ULK
activity as shown by the inhibited phosphorylation of the ULK
substrate ATG13 in vivo.
- DCC-3116 exhibited synergy with MAPK inhibitors in tumor growth
inhibition in mouse models.
A copy of each poster presentation is available at
www.deciphera.com.
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, providing evidence of TIE2 inhibition. Rebastinib
is currently being evaluated in a Phase 1b/2 clinical study in
combination with paclitaxel (NCT03601897) and in a Phase 1b/2
clinical study in combination with carboplatin (NCT03717415).
About DCC-3116
DCC-3116 is a potential first-in-class small molecule designed
to inhibit cancer autophagy, a key tumor survival mechanism, by
inhibiting the ULK kinase. Subject to favorable investigational new
drug (IND)-enabling studies and filing and activation of an IND
application, expected in mid-2020, Deciphera intends to develop
DCC-3116 for the potential treatment of mutant RAS cancers in
combination with inhibitors of downstream RAS effector targets
including RAF, MEK, or ERK inhibitors as well as with direct
inhibitors of mutant RAS.
About Deciphera Pharmaceuticals
Deciphera Pharmaceuticals is a clinical-stage biopharmaceutical
company focused on improving the lives of cancer patients by
addressing 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,
immuno-targeted agents designed to control the activation of
immunokinases that suppress critical immune system regulators, and
agents designed to inhibit reprogramming of cancer cell metabolism.
We have used our platform to develop a diverse pipeline of
tumor-targeted, immuno-targeted, and metabolism-targeted drug
candidates designed to improve outcomes for patients with cancer by
improving the quality, rate and/or durability of their responses to
treatment.
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 regarding the broad applicability of our
kinase switch control platform, the potential of our drug
candidates to address unmet needs in oncology, continuation of Part
2 of our Phase 1b/2 study of rebastinib in combination with
paclitaxel, advancing DCC-3116 through IND-enabling studies, and
the timing of the potential filing of an IND for DCC-3116, subject
to favorable IND enabling studies. 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 statements contain these identifying words. Any
forward-looking statements in this press release are based on
management’s current 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, 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, actions of regulatory agencies, any or all of which may
affect the initiation, timing and progress of clinical studies and
regulatory development and other risks identified in our SEC
filings, including our Quarterly Report on Form 10-Q for the
quarter ended June 30, 2019, and subsequent filings with the SEC.
We caution you not to place undue reliance on any forward-looking
statements, which speak only as of the date they are made. We
disclaim any obligation to publicly update or revise any such
statements to reflect any change in expectations or in events,
conditions or circumstances on which any such statements may be
based, or that may affect the likelihood that actual results will
differ from those set forth in the forward-looking statements. Any
forward-looking statements contained in this press release
represent our views only as of the date hereof and should not be
relied upon as representing its views as of any subsequent date. We
explicitly disclaim any obligation to update any forward-looking
statements.
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version on businesswire.com: https://www.businesswire.com/news/home/20191028005506/en/
Investor Relations: Jen Robinson Deciphera Pharmaceuticals, Inc.
jrobinson@deciphera.com 781-906-1112 Media: David Rosen Argot
Partners David.Rosen@argotpartners.com 212-600-1902
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