- QINLOCK Significantly Improved
Progression-Free Survival and Showed Clinically Meaningful Overall
Survival in Global INVICTUS Phase 3 Study -
- QINLOCK Approved via the U.S. FDA’s Project
Orbis Initiative -
Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) today announced
that Health Canada has authorized QINLOCK™ (ripretinib), a
switch-control tyrosine kinase inhibitor, for sale in Canada for
the treatment of adult patients with advanced gastrointestinal
stromal tumor (GIST) who have received prior treatment with
imatinib, sunitinib, and regorafenib. The QINLOCK New Drug
Submission was approved by Health Canada under Project Orbis, an
initiative of the U.S. Food and Drug Administration’s (FDA)
Oncology Center of Excellence designed to provide a framework for
concurrent submission and review of oncology products among
international partners. In May 2020, QINLOCK was approved by the
U.S. FDA for the treatment of adult patients with advanced GIST who
have received prior treatment with 3 or more kinase inhibitors,
including imatinib.
“Health Canada’s authorization of QINLOCK as part of FDA’s
Project Orbis marks an important milestone for GIST patients who
have long awaited a new therapeutic option specifically designed to
address this complex disease,” said Steve Hoerter, President and
Chief Executive Officer of Deciphera. “We would like to thank
Health Canada for their collaboration during the review process and
we look forward to bringing this important new therapy to patients
in Canada.”
Health Canada’s authorization was based on efficacy results from
the pivotal Phase 3 INVICTUS study of QINLOCK in patients with
advanced GIST as well as combined safety results from INVICTUS and
the Phase 1 study of QINLOCK. In INVICTUS, QINLOCK demonstrated a
median progression-free survival of 6.3 months compared to 1.0
month in the placebo arm and significantly reduced the risk of
disease progression or death by 85% (hazard ratio of 0.15,
p<0.0001). In addition, QINLOCK demonstrated a median overall
survival of 15.1 months compared to 6.6 months in the placebo arm
and reduced the risk of death by 64% (hazard ratio of 0.36).
The most common adverse reactions (≥20%) were alopecia, fatigue,
nausea, abdominal pain, constipation, myalgia, diarrhea, decreased
appetite, palmar-plantar erythrodysesthesia syndrome (PPES), and
vomiting. Adverse reactions resulting in permanent discontinuation
occurred in 8% of patients, dosage interruptions due to an adverse
reaction occurred in 24% of patients and dose reductions due to an
adverse reaction occurred in 7% of patients who received
QINLOCK.
About the INVICTUS Phase 3 Study
INVICTUS is a Phase 3 randomized, double-blind,
placebo-controlled, international, multicenter clinical study
evaluating the safety, tolerability, and efficacy of QINLOCK
compared to placebo in patients with advanced GIST whose previous
therapies have included imatinib, sunitinib, and regorafenib.
Patients were randomized 2:1 to either 150 mg of QINLOCK 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). The
median PFS in the study was 6.3 months compared to 1.0 month in the
placebo arm and significantly reduced the risk of disease
progression or death by 85% (hazard ratio of 0.15, p<0.0001).
Secondary endpoints as determined by independent radiologic review
using modified RECIST include Objective Response Rate (ORR) and
Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared
with 0% for placebo (p =0.0504). QINLOCK also demonstrated a median
OS of 15.1 months compared to 6.6 months in the placebo arm and
reduced the risk of death by 64% (hazard ratio of 0.36).
About QINLOCK (ripretinib)
QINLOCK is a 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. QINLOCK inhibits primary and
secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved
in GIST, as well as the primary exon 17 D816V mutation involved in
SM. QINLOCK also inhibits primary PDGFRα mutations in exons 12, 14,
and 18, including the exon 18 D842V mutation, involved in a subset
of GIST.
QINLOCK is approved by the U.S. FDA for the treatment of adult
patients with advanced GIST who have received prior treatment with
3 or more kinase inhibitors, including imatinib, and by Health
Canada for the treatment of adult patients with advanced
gastrointestinal stromal tumor (GIST) who have received prior
treatment with imatinib, sunitinib, and regorafenib.
Deciphera Pharmaceuticals is developing QINLOCK for the
treatment of KIT and/or PDGFRα-driven cancers, including GIST,
systemic mastocytosis, or SM, and other cancers. Deciphera
Pharmaceuticals has an exclusive license agreement with Zai Lab
(Shanghai) Co., Ltd. for the development and commercialization of
QINLOCK in Greater China (Mainland China, Hong Kong, Macau, and
Taiwan). Deciphera Pharmaceuticals retains development and
commercial rights for QINLOCK in the rest of the world.
U.S. Indication and Important Safety Information About
QINLOCK
Indications and Usage
QINLOCK (ripretinib) is a kinase inhibitor indicated for the
treatment of adult patients with advanced gastrointestinal stromal
tumor (GIST) who have received prior treatment with 3 or more
kinase inhibitors, including imatinib. For more information visit
QINLOCK.com.
Important Safety Information
There are no contraindications for QINLOCK.
Palmar-plantar erythrodysesthesia syndrome (PPES): In
INVICTUS, Grade 1-2 PPES occurred in 21% of the 85 patients who
received QINLOCK. PPES led to dose discontinuation in 1.2% of
patients, dose interruption in 2.4% of patients, and dose reduction
in 1.2% of patients. Based on severity, withhold QINLOCK and then
resume at same or reduced dose.
New Primary Cutaneous Malignancies: In INVICTUS,
cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the
85 patients who received QINLOCK with a median time to event of 4.6
months (range 3.8 to 6 months). In the pooled safety population,
cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients,
respectively. In INVICTUS, melanoma occurred in 2.4% of the 85
patients who received QINLOCK. In the pooled safety population,
melanoma occurred in 0.9% of 351 patients. Perform dermatologic
evaluations when initiating QINLOCK and routinely during treatment.
Manage suspicious skin lesions with excision and dermatopathologic
evaluation. Continue QINLOCK at the same dose.
Hypertension: In INVICTUS, Grade 1-3 hypertension
occurred in 14% of the 85 patients who received QINLOCK, including
Grade 3 hypertension in 7% of patients. Do not initiate QINLOCK in
patients with uncontrolled hypertension. Monitor blood pressure as
clinically indicated. Based on severity, withhold QINLOCK and then
resume at same or reduced dose or permanently discontinue.
Cardiac Dysfunction: In INVICTUS, cardiac failure
occurred in 1.2% of the 85 patients who received QINLOCK. In the
pooled safety population, cardiac dysfunction (including cardiac
failure, acute left ventricular failure, diastolic dysfunction, and
ventricular hypertrophy) occurred in 1.7% of 351 patients,
including Grade 3 adverse reactions in 1.1% of patients.
In INVICTUS, Grade 3 decreased ejection fraction occurred in
2.6% of the 77 patients who received QINLOCK and who had a baseline
and at least one post-baseline echocardiogram. Grade 3 decreased
ejection fraction occurred in 3.4% of the 263 patients in the
pooled safety population who received QINLOCK and who had a
baseline and at least one post-baseline echocardiogram.
In INVICTUS, cardiac dysfunction led to dose discontinuation in
1.2% of the 85 patients who received QINLOCK. The safety of QINLOCK
has not been assessed in patients with a baseline ejection fraction
below 50%. Assess ejection fraction by echocardiogram or MUGA scan
prior to initiating QINLOCK and during treatment, as clinically
indicated. Permanently discontinue QINLOCK for Grade 3 or 4 left
ventricular systolic dysfunction.
Risk of Impaired Wound Healing: QINLOCK has the potential
to adversely affect wound healing. Withhold QINLOCK for at least 1
week prior to elective surgery. Do not administer for at least 2
weeks following major surgery and until adequate wound healing. The
safety of resumption of QINLOCK after resolution of wound healing
complications has not been established.
Embryo-Fetal Toxicity: QINLOCK can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
and males with female partners of reproductive potential to use
effective contraception during treatment and for at least 1 week
after the final dose. Because of the potential for serious adverse
reactions in the breastfed child, advise women not to breastfeed
during treatment and for at least 1 week after the final dose.
QINLOCK may impair fertility in males of reproductive
potential.
Adverse Reactions: The most common adverse reactions
(≥20%) were alopecia, fatigue, nausea, abdominal pain,
constipation, myalgia, diarrhea, decreased appetite, PPES, and
vomiting. The most common Grade 3 or 4 laboratory abnormalities
(≥4%) were increased lipase and decreased phosphate.
The safety and effectiveness of QINLOCK in pediatric patients
have not been established.
Administer strong CYP3A inhibitors with caution. Monitor
patients who are administered strong CYP3A inhibitors more
frequently for adverse reactions. Avoid concomitant use with strong
CYP3A inducers.
Please click here to see the full U.S. Prescribing Information
for QINLOCK.
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 80%
of cases, or in PDGFRα kinase, representing approximately 6% 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 Deciphera Pharmaceuticals
Deciphera is a biopharmaceutical company focused on discovering,
developing and commercializing important new medicines to improve
the lives of people with cancer. We are leveraging our proprietary
switch-control kinase inhibitor platform and deep expertise in
kinase biology to develop a broad portfolio of innovative
medicines. In addition to advancing multiple product candidates
from our platform in clinical studies, QINLOCKTM is Deciphera’s
FDA-approved switch-control kinase inhibitor for the treatment of
fourth-line gastrointestinal stromal tumor (GIST). QINLOCK is also
authorized for fourth-line GIST in Canada. For more information,
please visit the Company’s website at www.deciphera.com.
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, our expectations
regarding bringing QINLOCK to patients in Canada, and the potential
benefit of QINLOCK to GIST patients. 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 severity and duration of the impact of
COVID-19 on our business and operations, including, without
limitation, commercial and clinical drug supply chain continuity
and the commercial launch of QINLOCK, our ability to successfully
demonstrate the efficacy and safety of our product candidates
including in later-stage studies, the preclinical and clinical
results for our product candidates, which may not support further
development of such product candidates, our ability to manage our
reliance on sole-source third parties such as our third party drug
substance and drug product contract manufacturers, actions of
regulatory agencies, our ability to commercialize QINLOCK and
execute on our marketing plans for any drugs or indications that
may be approved in the future, the inherent uncertainty in
estimates of patient populations and incidence and prevalence
estimates, competition from other products, our ability to obtain
and maintain reimbursement for any approved product and the extent
to which patient assistance programs are utilized, our ability to
comply with healthcare regulations and laws, our ability to obtain,
maintain and enforce our intellectual property rights, any or all
of which may affect the initiation, timing and progress of clinical
studies and the timing of and our ability to obtain additional
regulatory approvals, and make our investigational drugs and
QINLOCK available to patients, and to derive revenue from product
sales, and other risks identified in our Securities and Exchange
Commission (SEC) filings, including our Quarterly Report on Form
10-Q for the quarter ended March 31, 2020, 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.
Deciphera, Deciphera Pharmaceuticals, QINLOCK, the Deciphera
logo and the QINLOCK logo are trademarks of Deciphera
Pharmaceuticals, LLC.
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version on businesswire.com: https://www.businesswire.com/news/home/20200622005160/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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