- INVICTUS Achieved Primary Endpoint,
Ripretinib Significantly Improved Progression Free Survival (PFS)
Versus Placebo in Patients with Fourth-line and Fourth-line Plus
GIST -
- Median PFS for Ripretinib of 6.3 Months
Versus Placebo of 1.0 Month; Hazard Ratio of 0.15, p<0.0001-
- Company Expects to Submit an NDA to the FDA
in 1Q 2020 for the Treatment of Patients with Advanced GIST who
have Received Prior Treatment with Imatinib, Sunitinib and
Regorafenib -
- Company to Host Conference Call Today at 8:00
AM ET -
Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage
biopharmaceutical company focused on addressing key mechanisms of
tumor drug resistance, today announced positive top-line data from
the INVICTUS pivotal Phase 3 clinical study of ripretinib, a
broad-spectrum KIT and PDGFRα inhibitor, in patients with
fourth-line and fourth-line plus gastrointestinal stromal tumors
(GIST).
“There is a dire unmet need for new therapies that can deliver
effective disease control for patients with advanced GIST who have
failed currently approved treatment options,” said Margaret von
Mehren, MD, Department of Medical Oncology, Fox Chase Cancer
Center, Philadelphia, Pennsylvania. “These top-line data from a
Phase 3, randomized, placebo-controlled study are highly impressive
and suggest that ripretinib’s approach of targeting the broad
spectrum of KIT and PDGFRα mutations known to drive GIST can
significantly improve progression free survival in the most heavily
pretreated patients. Particularly notable is the magnitude of
benefit observed for overall survival in this study.”
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. The INVICTUS study achieved its primary endpoint of
improved PFS as determined by blinded independent central
radiologic review using modified Response Evaluation Criteria in
Solid Tumors (RECIST) version 1.1.
In the INVICTUS study, ripretinib demonstrated a median PFS of
6.3 months (27.6 weeks) compared to 1.0 month (4.1 weeks) in the
placebo arm and significantly reduced the risk of disease
progression or death by 85% (HR of 0.15, p<0.0001) compared to
placebo.
For the key secondary endpoint of objective response rate (ORR),
as determined by blinded independent central radiologic review
using modified RECIST version 1.1, ripretinib demonstrated an ORR
of 9.4% compared with 0% for placebo (p-value=0.0504), which was
not statistically significant. Ripretinib in this study also showed
a clinically meaningful improvement over placebo in terms of the
secondary endpoint overall survival (OS) (median OS 15.1 months vs.
6.6 months, HR = 0.36, nominal p-value=0.0004). Since statistical
significance was not achieved for 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 of ORR
is statistically significant. The OS data for the placebo arm
includes patients taking placebo who, following progression, were
crossed-over to ripretinib treatment.
Ripretinib was generally well tolerated and the adverse event
results in INVICTUS were consistent with data from previously
presented Phase 1 study results. Grade 3 or 4 treatment-emergent
adverse events (TEAEs) occurred in 42 (49%) patients on the
ripretinib arm compared to 19 (44%) on the placebo arm. Grade 3 or
4 TEAEs >5% of patients in the ripretinib arm were anemia (9%;
n=8), abdominal pain (7%; n=6) and hypertension (7%; n=6). Grade 3
or 4 TEAEs >5% of patients in the placebo arm were anemia (14%;
n=6). The below table lists TEAEs >15% in the ripretinib arm
compared to placebo.
INVICTUS Phase 3 Clinical
Study
Treatment Emergent Adverse
Event
Placebo
Ripretinib
(N=43)(1)
150mg Daily
(N=85)(1)
Any event
42 (98
%)
84 (99
%)
Alopecia
2 (5
%)
44 (52
%)
Fatigue
10 (23
%)
36 (42
%)
Nausea
5 (12
%)
33 (39
%)
Abdominal pain
13 (30
%)
31 (36
%)
Constipation
8 (19
%)
29 (34
%)
Myalgia
5 (12
%)
27 (32
%)
Diarrhea
6 (14
%)
24 (28
%)
Decreased appetite
9 (21
%)
23 (27
%)
Palmar-plantar erythrodysaesthesia
syndrome
0
18 (21
%)
Vomiting
3 (7
%)
18 (21
%)
Headache
2 (5
%)
16 (19
%)
Weight decreased
5 (12
%)
16 (19
%)
Arthralgia
2 (5
%)
15 (18
%)
Blood bilirubin increased
0
14 (16
%)
Oedema peripheral
3 (7
%)
14 (16
%)
Muscle spasms
2 (5
%)
13 (15
%)
Notes to table: (1) Safety population
includes 128 patients. One patient was randomized to placebo but
did not receive study drug.
“Today’s announcement represents a significant milestone in our
mission to deliver important new medicines for the treatment of
cancer,” said Steve Hoerter, President and Chief Executive Officer
of Deciphera. “On behalf of the entire Deciphera team, I would like
to thank the patients, their caregivers and the healthcare
professionals who participated in the INVICTUS study. The data from
INVICTUS reinforce our belief that ripretinib has the potential to
transform the treatment of GIST, and our focus now turns to working
closely with the FDA as they evaluate ripretinib for those patients
with GIST who, having failed all currently approved therapies, are
in desperate need of a treatment option.”
Based on the positive INVICTUS data, the Company expects to
submit a New Drug Application (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.
Additional results from the INVICTUS Phase 3 clinical study are
expected to be presented at an upcoming medical meeting.
Conference Call and Webcast
Deciphera will host a conference call and webcast to discuss the
results of the INVICTUS Phase 3 clinical study today, August 13,
2019 at 8:00 AM ET. To access the live call by phone please dial
866-930-5479 (domestic) or 409-216-0603 (international); the
conference ID is 8859018. A live audio webcast of the event and
accompanying slides may also be accessed through the “Investors”
section of Deciphera’s website at www.deciphera.com. A replay of
the webcast will be available for 30 days following the event.
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 GIST
Gastrointestinal stromal tumor (GIST) is a cancer affecting the
digestive tract or nearby structures within the abdomen, most often
presenting in the stomach or small intestine. GIST is the most
common sarcoma of the gastrointestinal tract, with approximately
4,000 to 6,000 new GIST cases each year in the United States and a
similar incidence rate in European and other countries. Most cases
of GIST are driven by a spectrum of mutations. The most common
primary mutations are in KIT kinase, representing approximately 75%
to 80% of cases, or in PDGFRα kinase, representing approximately 5%
to 10% of cases. Current therapies are unable to inhibit the full
spectrum of primary and secondary mutations, which drives
resistance and disease progression. Estimates for 5-year survival
range from 48% to 90%, depending on the stage of the disease at
diagnosis.
About Ripretinib
Ripretinib is an investigational 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 other cancers.
Ripretinib was specifically designed to improve the treatment of
patients with GIST by inhibiting a broad spectrum of mutations in
KIT and PDGFRα. Ripretinib is a KIT and PDGFRα inhibitor that
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
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.
Availability of Other Information About Deciphera
Pharmaceuticals
Investors and others should note that Deciphera Pharmaceuticals
communicates with its investors and the public using its company
website (www.deciphera.com), including but not limited to investor
presentations and scientific presentations, Securities and Exchange
Commission filings, press releases, public conference calls and
webcasts. The information that Deciphera Pharmaceuticals posts on
these channels and websites could be deemed to be material
information. As a result, Deciphera Pharmaceuticals encourages
investors, the media and others interested in Deciphera
Pharmaceuticals to review the information that it posts on these
channels, including Deciphera Pharmaceuticals’ investor relations
website, on a regular basis. This list of channels may be updated
from time to time on Deciphera Pharmaceuticals' investor relations
website and may include other social media channels than the ones
described above. The contents of Deciphera Pharmaceuticals' website
or these channels, or any other website that may be accessed from
its website or these channels, shall not be deemed incorporated by
reference in any filing under the Securities Act of 1933, as
amended.
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 reporting additional data from
our INVICTUS pivotal Phase 3 study of ripretinib in GIST patients
at an upcoming medical meeting, the potential for the results of
our INVICTUS pivotal Phase 3 clinical study to support a 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 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, 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/20190813005228/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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