- Median Progression Free Survival (mPFS) of 46
Weeks for the Second-Line Gastrointestinal Stromal Tumors (GIST)
Cohort from the Phase 1 Study of Ripretinib in Patients Receiving
150 mg QD as Starting Dose -
- DCC-3014 Phase 1 Data Demonstrated
Tolerability, Pharmacokinetics and Biomarker Mechanistic
Proof-of-Concept in Patients with Advanced Malignancies -
Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage
biopharmaceutical company addressing key mechanisms of tumor drug
resistance, today announced the presentation of updated results
from its ongoing Phase 1 study of ripretinib, a broad-spectrum KIT
and PDGFRα inhibitor, in patients with second-line through
fourth-line plus GIST, as well as its Phase 1 study of DCC-3014, an
oral inhibitor of CSF1R, in patients with advanced solid tumors.
The data are being presented today at the AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer
Therapeutics in Boston.
“These updated results continue to underscore the potential of
our diverse pipeline of product candidates, all generated using our
proprietary kinase switch control inhibitor platform, to improve
the lives of cancer patients,” said Matthew L. Sherman, M.D.,
Executive Vice President and Chief Medical Officer of Deciphera.
“Of note, we believe ripretinib continues to demonstrate strong
clinical benefit in post-imatinib GIST patients, particularly in
the second-line setting. These results bolster our confidence in
the ongoing INTRIGUE pivotal Phase 3 clinical study, which is
designed to support potential regulatory approvals in patients with
second-line GIST.”
Ripretinib
Updated results from the Company’s ongoing Phase 1 study of
ripretinib in patients with second-line through fourth-line plus
GIST included data from 142 GIST patients receiving 150 mg of
ripretinib once daily (QD) as the starting dose, which is the dose
being utilized in the Company’s INVICTUS and INTRIGUE
registration-enabling studies, as of an August 10, 2019 data cutoff
date. The table below includes local, investigator-assessed
objective response rate (ORR) by best response as determined by
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
median duration of response, median progression free survival
(mPFS) and mean treatment duration.
Line of Therapy
2nd Line
(n=31)
3rd Line
(n=28)
≥4th Line
(n=83)
ORR (confirmed responses only)
19%
14%
7%
Median Duration of Response
80 weeks
NE(1)
76 weeks
mPFS
46 weeks
36 weeks
24 weeks
Mean Treatment Duration(2)
56 weeks
58 weeks
45 weeks
(1) NE = not estimable; (2) Includes 64
patients who elected for intra-patient dose escalation from 150 mg
QD to 150 mg twice daily (BID).
Data from GIST patients receiving ≥ 100 mg
of ripretinib daily (n=178) in the ongoing Phase 1 study, as of an
August 10, 2019 cutoff date, including 2nd line (n=37), 3rd line
(n=31), and ≥4th line (n=110) patients were (a) ORR (confirmed
responses only): 2nd line (22%), 3rd line (13%), ≥4th line (7%);
(b) median duration of response: 2nd line (80 weeks), 3rd line
(NE), ≥4th line (48 weeks); (c) mPFS: 2nd line (46 weeks), 3rd line
(40 weeks), ≥4th line (24 weeks); (d) mean treatment duration
(includes 72 patients who elected for intra-patient dose escalation
to 150 mg BID): 2nd line (53 weeks), 3rd line (54 weeks), ≥4th line
(48 weeks).
Ripretinib was generally well tolerated and the updated adverse
events were consistent with previously presented Phase 1 data in
patients with GIST. Grade 3 or 4 treatment-emergent adverse events
(TEAEs) in >5% of patients were increase in lipase level (n=25;
18%), anemia (n=11; 8%), and abdominal pain (n=11; 8%).
DCC-3014
The Company’s Phase 1 study of DCC-3014 was designed to evaluate
the safety, pharmacokinetics and pharmacodynamics of multiple doses
of DCC-3014 in patients with advanced solid tumors. The Company
expects to present preliminary data from initial tenosynovial giant
cell tumor (TGCT) patients at the 2019 Connective Tissue Oncology
Society (CTOS) Annual Meeting being held November 13-16 in Tokyo,
Japan.
- As of the data cut-off date of September 10, 2019, increasing
doses of DCC-3014 were assessed in seven dose cohorts across 36
patients with advanced solid tumor tumors. This included one dose
cohort that received 10 mg once daily and six dose cohorts that
received a three to five day loading dose regimen at doses of up to
50 mg followed by a schedule of daily, once-weekly or twice-weekly
maintenance dosing with DCC-3014.
- Data demonstrated dose-proportional exposure for DCC-3014 and
exposure to DCC-3014 was associated with an increase in plasma CSF1
and IL-34, rapid and sustained reduction of CD16+ monocytes in
peripheral blood, and substantial decreases in CD163+ macrophages
in tumor.
- DCC-3014 was generally well-tolerated, with most
treatment-emergent adverse events (TEAEs) Grade 1 or 2. Most common
related TEAEs ≥10% were fatigue (n=6;17%), diarrhea (n=4; 11%), and
nausea (n=4; 11%). Grade 3 or 4 related TEAEs occurred in 4
patients, which were grade 3 aspartate aminotransferase (AST)
increase, grade 4 lipase increase, grade 3 amylase increase, and
grade 3 colitis. Serious adverse events were reported in 17
patients; none of which were related to DCC-3014.
- The dose escalation evaluation is ongoing to determine a
recommended phase 2 dose for advanced solid tumors and diffuse-type
TGCT.
A copy of each presentation is available at
www.deciphera.com/science/presentation-publications/.
About Ripretinib
Ripretinib is an investigational tyrosine kinase switch control
inhibitor that was engineered to broadly inhibit KIT and PDGFRα
mutated kinases by using a unique dual mechanism of action that
regulates the kinase switch pocket and activation loop. Ripretinib
is currently in clinical development for the treatment of KIT
and/or PDGFRα-driven cancers, including gastrointestinal stromal
tumors, or GIST, systemic mastocytosis, or SM, and other cancers.
Ripretinib inhibits initiating and secondary KIT mutations in exons
9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary
D816V exon 17 mutation involved in SM. Ripretinib also inhibits
primary PDGFRα mutations in exons 12, 14 and 18, including the exon
18 D842V mutation, involved in a subset of GIST. In June 2019, the
U.S. FDA granted Fast Track Designation to ripretinib for the
treatment of patients with advanced GIST who have received prior
treatment with imatinib, sunitinib and regorafenib. For more
information about the Company’s clinical trials with ripretinib,
please visit www.clinicaltrials.gov.
Deciphera Pharmaceuticals has an exclusive license agreement
with Zai Lab (Shanghai) Co., Ltd. for the development and
commercialization of ripretinib in Greater China (Mainland China,
Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains
development and commercial rights for ripretinib in the rest of the
world.
About DCC-3014
DCC-3014 is an investigational, orally administered, potent and
highly selective inhibitor of CSF1R. DCC-3014 was designed using
the Company’s proprietary switch control kinase inhibitor platform
to selectively bind to the CSF1R switch pocket. DCC-3014 has
greater than 100-fold selectivity for CSF1R over other closely
related kinases and has an even greater selectivity for CSF1R over
approximately 300 other human kinases. CSF1R controls the
differentiation and function of macrophages including Tumor
Associated Macrophages (TAMs) whose density within certain tumors
including cancers of the breast, cervix, pancreas, bladder and
brain correlates with poor prognosis. Tumors induce TAMs to
suppress a natural immune response mediated by cytotoxic T-cells, a
type of lymphocyte that would otherwise eradicate the tumor; a
process known as macrophage checkpoints. Through inhibition of
CSF1R, DCC-3014 has in preclinical studies demonstrated potent
macrophage checkpoint inhibition as both a single agent and in
combination with PD1 inhibitors. DCC-3014 is currently being
evaluated in a Phase 1 clinical study. For more information about
the clinical trial design please visit www.clinicaltrials.gov
(NCT03069469).
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 and
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 our updated Phase 1 study of
ripretinib in patients with GIST to support our pivotal Phase 3
INTRIGUE study in second-line GIST patients, the potential of our
pipeline drug candidates to improve the lives of patients with
cancer, and the expectation to present additional data from our
Phase 1 study of DCC-3014 in patients with diffuse-type
tenosynovial giant cell tumor at an upcoming medical meeting. 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, our ability to timely complete
and prepare the information required for and file an NDA for
ripretinib, our ability to manage and our reliance on third parties
such as our third party drug substance and drug product contract
manufacturers, actions of regulatory agencies, any or all of which
may affect the initiation, timing and progress of clinical studies
and the timing of and our ability to obtain regulatory approval, if
at all, and make our investigational drugs available to patients,
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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191029005808/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
Deciphera Pharmaceuticals (NASDAQ:DCPH)
Historical Stock Chart
From Aug 2024 to Sep 2024
Deciphera Pharmaceuticals (NASDAQ:DCPH)
Historical Stock Chart
From Sep 2023 to Sep 2024