Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage
biopharmaceutical company addressing key mechanisms of tumor drug
resistance, today announced the late-breaking presentation of
results from the INVICTUS pivotal Phase 3 clinical study of
ripretinib in patients with advanced gastrointestinal stromal
tumors (GIST) in an oral session at the European Society for
Medical Oncology (ESMO) 2019 Congress.
“For GIST patients who have failed currently approved agents,
there exists an urgent need for effective and well-tolerated
treatment options,” said Margaret von Mehren, MD, Department of
Medical Oncology, Fox Chase Cancer Center, Philadelphia,
Pennsylvania. “With a statistically significant improvement
observed in progression free survival compared with placebo, and a
clinically meaningful increase in overall survival compared with
placebo, ripretinib represents a potential standard of care for
patients harboring a broad spectrum of mutations known to drive
GIST in patients who have no approved treatment options.”
“Results from the INVICTUS study support our belief that
ripretinib has the potential to transform the current treatment
landscape for advanced GIST,” said Steve Hoerter, President and
Chief Executive Officer of Deciphera. “We are now working with the
FDA as we prepare the NDA submission for ripretinib, which we
expect in the first quarter of 2020.”
Today’s presentation featured new data as well as top-line
results previously announced by the Company in August 2019. A copy
of the presentation will be available following the session at
www.deciphera.com.
INVICTUS Study Results
The INVICTUS Phase 3 clinical study is a randomized (2:1),
double-blind, placebo-controlled, international, multicenter study
to evaluate the safety, tolerability, and efficacy of ripretinib
compared to placebo in 129 patients with advanced GIST whose
previous therapies have included at least imatinib, sunitinib, and
regorafenib. As previously reported, the study achieved the primary
endpoint of improved progression free survival (PFS) compared to
placebo in patients with fourth-line and fourth-line plus GIST, as
determined by blinded independent central radiologic review using
modified Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1.
Progression Free Survival (PFS)
Ripretinib significantly reduced the risk of disease progression
or death by 85% compared to placebo and demonstrated a median PFS
of 6.3 months compared to 1.0 month in the placebo arm (HR=0.15,
95% CI (0.09,0.25), p<0.0001). This PFS benefit was consistent
across all assessed patient subgroups.
Objective Response Rate (ORR) and Duration of
Response
Eight patients (9.4%) had a confirmed objective response with
ripretinib (p=0.0504) compared to no confirmed responses in the
placebo arm, as measured by blinded independent central review,
which was not statistically significant. As of the cutoff date of
May 31, 2019, the median duration of response had not been reached
with seven of the eight patients still responding to treatment. All
responders had partial responses.
Overall Survival (OS)
Ripretinib reduced the risk of death by 64% compared to placebo
and demonstrated a median OS of 15.1 months vs. 6.6 months in the
placebo arm (HR=0.36, 95% CI (0.20,0.62), nominal p=0.0004). Since
statistical significance was not achieved for the secondary
endpoint of ORR, the hypothesis testing of OS was not formally
performed. According to the pre-specified hierarchical testing
procedure of the endpoints, the hypothesis testing of OS cannot be
formally conducted unless the test for ORR is statistically
significant.
Safety
Ripretinib was generally well tolerated and the adverse events
observed in INVICTUS were consistent with data from previously
presented Phase 1 study results. Treatment-emergent adverse events
(TEAEs) occurred in 99% of patients on the ripretinib arm compared
to 98% on the placebo arm. Grade 3 or 4 TEAEs occurred in 49% of
patients on the ripretinib arm compared to 44% on the placebo arm.
Grade 3 or 4 TEAEs greater than 5% of patients on the ripretinib
arm were anemia (9%), abdominal pain (7%) and hypertension (7%).
Grade 3 or 4 TEAEs greater than 5% of patients on the placebo arm
were anemia (14%). TEAEs leading to dose reduction occurred in 7%
of patients on the ripretinib arm compared to 2% on the placebo
arm. TEAEs leading to dose interruption occurred in 24% of patients
on the ripretinib arm compared to 21% on the placebo arm. TEAEs
leading to study treatment discontinuation occurred in 8% of
patients on the ripretinib arm compared to 12% of patients on the
placebo arm. TEAEs leading to death occurred in 6% of patients on
the ripretinib arm compared to 23% on the placebo arm.
New Drug Application (NDA) Submission
Based on the positive INVICTUS data, the Company expects to
submit an NDA to the U.S. Food and Drug Administration (FDA) for
ripretinib for the treatment of patients with advanced GIST who
have received prior treatment with imatinib, sunitinib and
regorafenib in the first quarter of 2020.
About the INVICTUS Phase 3 Study
The INVICTUS Phase 3 clinical study is a randomized,
double-blind, placebo-controlled, international, multicenter study
to evaluate the safety, tolerability, and efficacy of ripretinib
compared to placebo in patients with advanced GIST whose previous
therapies have included imatinib, sunitinib, and regorafenib. This
study was designed to provide evidence of clinical benefit in
fourth-line and fourth-line plus patients with GIST that would be
required to secure a regulatory approval. Patients were randomized
2:1 to either 150 mg of ripretinib or placebo once daily. The
primary efficacy endpoint is progression-free survival (PFS) as
determined by independent radiologic review using modified Response
Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints
as determined by independent radiologic review using modified
RECIST include Objective Response Rate (ORR), Time to Tumor
Progression (TTP) and Overall Survival (OS). See
www.clinicaltrials.gov for further information (NCT03353753).
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.
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 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, 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.
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 potential for the results of our INVICTUS pivotal
Phase 3 clinical study to support an NDA submission, the timing of
our planned NDA submission for fourth and fourth-line plus GIST,
the potential for ripretinib and our other drug candidates based on
our kinase switch control inhibitor platform to provide clinical
benefit, impact current treatment paradigms and landscape and treat
cancers such as GIST and other possible indications, and
preparations for seeking regulatory approval for and making
ripretinib available to patients with fourth-line and fourth-line
plus GIST, if approved. 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20190930005477/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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