Deciphera Pharmaceuticals Reports Updated Interim Phase 1 Clinical Study Results with DCC-2618 at The 2018 American Society of Clinical Oncology Annual Meeting (ASCO) and Provides Additional Clinical and Regulatory Updates on DCC-2618
- Initial Objective Response Rates and Disease Control Rates in
Second and Third Line GIST Patients Exceed Previously Published Results
of Registrational Trials for Currently Approved Therapies -
- Mutational Profiling Data Across Second, Third and Fourth Line GIST
Patients Demonstrates the Breadth of KIT Mutations and Ability of
DCC-2618 to Reduce Mutant Allele Frequency (MAF) -
- Initiation of a Phase 3 Trial in Second Line GIST Patients Expected
in 2018 -
- Interim Results with DCC-2618 Demonstrate Robust Clinical
Activity in Heavily Pretreated GIST Patients, Including Patients
Previously Treated with the Investigational Agent avapritinib (BLU-285) -
Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage
biopharmaceutical company focused on addressing key mechanisms of tumor
drug resistance, announced the presentation today of updated data from
its ongoing Phase 1 clinical trial of DCC-2618, the company's
broad-spectrum KIT and PDGFRα inhibitor, in patients with
gastrointestinal stromal tumors (GIST) at the American Society of
Clinical Oncology (ASCO) Annual Meeting 2018, in Chicago, Illinois and
provided additional clinical and regulatory updates on DCC-2618.
Suzanne George, M.D. Assistant Professor of Medicine, Harvard Medical
School and Clinical Director, Center for Sarcoma and Bone Oncology,
Dana-Farber Cancer Institute presented the poster titled "Mutational
Profile of Drug Resistant GIST Patients Enrolled in the Phase 1 Study of
DCC-2618". In addition to describing the mutational profile of KIT in
GIST patients, the poster includes details of locally-read Objective
Response Rates (ORR) and Disease Control Rates (DCR) as assessed by
Response Evaluation Criteria in Solid Tumors (RECIST) in second, third,
and fourth and fourth line plus GIST patients that received DCC-2618 at
doses of ≥100mg daily for at least one 28-day cycle prior to February 2,
2018:
Line of Therapy | GIST Patients (n) | DCR at 3 Months | ORR | |||
2nd Line1 | 25 | 79% | 24% | |||
3rd Line1 | 29 | 82% | 24% | |||
≥4th Line | 91 | 64% | 9% | |||
Total | 145 | 70% | 15% |
1 46 of 54 second and third line patients received
150mg once daily dose.
The combined 24% ORR and 80% 3-month DCR in second and third line
patients receiving DCC-2618 at doses of ≥100mg per day exceeds
previously published results of registrational trials for the currently
approved therapies for second line (sunitinib) and third line
(regorafenib), which have reported ORRs of 7.0% and 4.5%, respectively,
and levels of disease control of 60% and 53%, respectively.
"The preliminary data presented today on DCC-2618's activity in second
and third line GIST patients is very encouraging and supports the
planned initiation later this year of our Phase 3 trial, INTRIGUE, in
second line GIST patients," said Michael D. Taylor, Ph.D., President and
Chief Executive Officer of Deciphera. "The mutational profiling data
across second, third and fourth line GIST patients observed in the Phase
1 study also demonstrates the need for the broadest spectrum of KIT
inhibition in all GIST patients who previously received imatinib."
"We are very pleased with the results presented today demonstrating
DCC-2618's potential to provide improved clinical benefit for not only
heavily pre-treated patients, but also for second and third line GIST
patients," said Oliver Rosen, M.D. Chief Medical Officer of Deciphera.
"Combined with the tolerability data presented at AACR in April 2018,
these results demonstrate the potential of DCC-2618 as an effective and
well tolerated therapy for a wide range of GIST patients."
Highlights from the poster presentation include:
-
Initial Objective Response Rates and Disease Control Rates with
DCC-2618 at Doses of ≥100mg Daily in Second and Third Line GIST
Patients Exceed Previously Published Results of Registrational Trials
for Currently Approved Therapies, as well as the Results Observed in
Heavily Pre-Treated GIST Patients Receiving DCC-2618:-
24% ORR with DCC-2618 observed to date in second and third line
GIST patients is higher than that reported for sunitinib in second
line patients (7.0%) or regorafenib in third line patients (4.5%). -
These interim results show improved ORR and 3-month DCR in second
line GIST patients treated with DCC-2618 compared to fourth and
fourth line plus GIST patients treated with DCC-2618.
-
24% ORR with DCC-2618 observed to date in second and third line
-
Mutational Profiling Data Across Second, Third and Fourth Line GIST
Patients Demonstrates the Breadth of KIT Mutations in GIST and the
Ability of DCC-2618 to Reduce KIT Mutant Allele Frequency (MAF):-
Resistance mutations in KIT in exons 13, 14, 17 and 18, or a
combination thereof, occurs in second, third and, fourth and
fourth line plus patients. -
The KIT mutational profile in both tumors and plasma at baseline
in GIST patient supports the need for a broad-spectrum KIT
inhibitor in all post-imatinib lines of therapy. -
57 of 73 patients (78%) receiving DCC-2618 at doses of ≥100 mg
daily demonstrated reductions in KIT MAF of more than 50%.
-
Resistance mutations in KIT in exons 13, 14, 17 and 18, or a
In addition, the company is providing the following clinical and
regulatory updates on DCC-2618:
-
Planned Initiation of a Phase 3 Trial in Second Line GIST Patients
in 2018-
Preliminary efficacy results in second line patients together with
recently presented tolerability data at the recommended phase 2
dose (RP2D) of 150mg QD support the planned, randomized Phase 3
trial, INTRIGUE, in second line GIST. -
Following discussions with regulatory authorities in the United
States and in Europe, the company has designed INTRIGUE as a
randomized, multicenter, open-label, Phase 3 trial in second line
GIST. This registration study is expected to enroll approximately
350 patients who will be randomized 1:1 to either DCC-2618 or
sunitinib, the current standard of care in second line; with
median progression free survival as the primary endpoint.
-
Preliminary efficacy results in second line patients together with
-
Interim Results with DCC-2618 at Doses of ≥100mg Daily Demonstrate
Robust Clinical Activity in Heavily Pretreated GIST Patients,
Including Patients Previously Treated with the Investigational Agent
avapritinib (BLU-285):-
10 patients with KIT-driven GIST who previously received
avapritinib were enrolled and treated with DCC-2618 as of January
31, 2018. -
6 out of 10 (60%) of these patients achieved stable disease as
best response by RECIST during treatment with DCC-2618. In
addition, one patient achieved stable disease following
intra-patient dose escalation to 150mg BID. -
5 out of 10 (50%) of these patients were on study as of April 18,
2018. -
3 out of 10 (30%) of these patients received DCC-2618 for more
than six months. Two of these patients achieved continued stable
disease and remain on study as of April 18, 2018. The third
patient with progressive disease was dose escalated and was
reported as off study as of April 18, 2018.
-
10 patients with KIT-driven GIST who previously received
A copy of the poster presentation will be available on the Science
section of the Deciphera website under "Presentations and Publications"
at www.deciphera.com.
About DCC-2618
DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical
development for the treatment of KIT and/or PDGFRα-driven cancers,
including gastrointestinal stromal tumors, or GIST, systemic
mastocytosis, or SM, and glioblastoma multiforme. DCC-2618 was
specifically designed to improve the treatment of GIST patients by
inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is
a KIT and PDGFRα inhibitor that blocks 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. DCC-2618 also
inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the
exon 18 D842V mutation, involved in a subset of GIST.
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 the planned
initiation later this year of our Phase 3 trial, INTRIGUE, in second
line GIST patients; the need for a broad-spectrum KIT inhibitor in all
post-imatinib lines of therapy; potential for DCC-2618 as an effective
and well tolerated therapy to treat a wide range of patients with GIST,
SM, glioblastoma multiforme and other diseases; statements regarding the
potential benefits to patients of DCC-2618; statements regarding plans
and timelines for the clinical development of DCC-2618; and Deciphera
Pharmaceuticals' strategy, business plans and focus. The words "designed
to," "may," "will," "could," "would," "should," "expect," "plan,"
"approximate," "anticipate," "intend," "believe," "estimate," "predict,"
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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, statements regarding the
potential for DCC-2618 to treat GIST SM, glioblastoma multiforme and
other diseases; statements regarding the potential benefits to patients
of DCC-2618; statements regarding plans and timelines for the clinical
development of DCC-2618; and Deciphera Pharmaceuticals' strategy,
business plans and focus. These and other risks and uncertainties are
described in greater detail in the section entitled "Risk Factors" in
Deciphera Pharmaceuticals' most recent annual report on Form 10-K, and
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