- Clinically Meaningful Benefit Observed
in Patients Receiving QINLOCK Following Progression on Placebo
-
- Data Featured at the ESMO World Congress on
Gastrointestinal Cancer 2020 Virtual Meeting -
Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) today announced
the presentation of new data from an exploratory analysis of
progression-free survival (PFS) and overall survival (OS) for
patients who crossed over to QINLOCK therapy following disease
progression in the INVICTUS pivotal Phase 3 study. The INVICTUS
study evaluated QINLOCK in adult patients with fourth-line
gastrointestinal stromal tumor (GIST). The results were featured in
an oral presentation at the European Society for Medical Oncology
(ESMO) World Congress on Gastrointestinal (GI) Cancer 2020 Virtual
Meeting in a presentation titled, “Efficacy and safety of
ripretinib as ≥4th-line therapy for patients with gastrointestinal
stromal tumor (GIST) following crossover from placebo: Analyses
from INVICTUS” (Abstract ID O-13). The data presented showed that
patients who crossed over to the open-label extension to receive
treatment with QINLOCK demonstrated a median PFS of 4.6 months and
an OS benefit of 11.6 months.
“The data presented today further reinforce the potential of
QINLOCK to provide meaningful clinical benefit to patients with
advanced GIST,” said César Serrano, MD, PhD, Head of the Sarcoma
Translational Research Group at the Vall d'Hebron Institute of
Oncology. “QINLOCK represents a new standard of care for patients
with GIST who have received 3 prior treatments.”
“On the heels of QINLOCK’s recent approval in the U.S. and
Canada in patients with fourth-line GIST, we are excited to add to
the body of evidence supporting its potential as a new standard of
care in this setting,” said Matthew L. Sherman, MD, Executive Vice
President and Chief Medical Officer of Deciphera. “GIST is a highly
complex disease for which we specifically designed QINLOCK and we
are committed to ensuring it is able to reach as many appropriate
patients as possible.”
INVICTUS Crossover Data Analysis
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 QINLOCK
compared to placebo in 129 patients with advanced GIST whose
previous therapies have included at least imatinib, sunitinib, and
regorafenib. The Company previously reported results from the
randomized portion of the INVICTUS study, in which QINLOCK
significantly improved PFS and showed a clinically meaningful OS
benefit.
Following disease progression, patients randomized to the
placebo arm were eligible to cross over to an open-label extension
portion of the study to receive treatment with 150 mg of QINLOCK
once daily. Of the 44 patients randomized to receive placebo during
the double-blind treatment period, a total of 29 patients crossed
over and were treated with QINLOCK. Based on an exploratory
analysis of the data, patients treated in the open-label extension
demonstrated a median PFS of 4.6 months, from initiation of
treatment with QINLOCK to progression or death. Of note, two
patients achieved partial responses, with responses observed as
early as one month following initiation of QINLOCK therapy. In
addition, patients who crossed over demonstrated an OS benefit of
11.6 months, as measured from initial study randomization and
including all time periods, including dose escalations. Treatment
with QINLOCK was generally well tolerated and the adverse events
observed were consistent with those in the double-blind portion of
INVICTUS. These exploratory results reinforce the potential for
QINLOCK to provide meaningful benefit to GIST patients.
A copy of the presentation is available at
www.deciphera.com/science/presentation-publications/.
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 switch-control tyrosine kinase 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
systemic mastocytosis, or 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 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, 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 GIST. 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 the potential benefit of QINLOCK to GIST patients, the
potential for QINLOCK to become a standard of care in fourth-line
GIST, and our commitment to ensuring appropriate patients receive
QINLOCK. 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,
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,
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 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/20200702005455/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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