CAMBRIDGE, Mass., Nov. 30, 2016 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a leader in discovering
and developing targeted kinase medicines for patients with
genomically defined diseases, today announced data from its ongoing
Phase 1 clinical trial evaluating BLU-285, an investigational
medicine for the treatment of patients with advanced
gastrointestinal stromal tumors (GIST). These data provide
proof-of-concept for BLU-285, a potent, highly selective inhibitor
of D842V mutant PDGFRα and Exon 17 mutant KIT. The data will be
presented on Thursday, December 1,
2016 at the 28th EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics in Munich, Germany (EORTC-NCI-AACR).
"The clinical activity observed to date in the dose escalation
portion of this Phase 1 study is promising," said Michael Heinrich, M.D., Oregon Health &
Science University, an investigator for the clinical trial.
"Advanced GIST is a devastating illness, marked by rapid disease
progression. Seeing tumor shrinkage in 14 out of 15 PDGFRα-driven
GIST patients at this point in the study is notable. I am also
excited to see tumor shrinkage in four out of the six KIT-driven
GIST patients treated at the higher dose levels, indicating the
potential for increased clinical activity as we continue to
dose-escalate. Given these encouraging early data for this
investigational medicine, I believe BLU-285 could be transformative
for patients with advanced GIST."
"These data help to validate Blueprint Medicines' ability to
craft targeted kinase inhibitors and to achieve rapid
proof-of-concept for our investigational therapies in
genomically-defined populations," said Andy
Boral, M.D., Chief Medical Officer at Blueprint Medicines.
"We are encouraged by the early evidence of clinical activity, with
the majority of patients achieving stable disease or a partial
response, and some patients having durable tumor reduction lasting
at least eight months. I am also pleased that BLU-285 has been
well-tolerated to date and that the pharmacokinetic profile
supports once daily dosing. We continue to believe that BLU-285 has
the potential to significantly impact the treatment paradigm for
patients with GIST."
Data from the Ongoing Phase 1 Clinical Trial
BLU-285 is currently being evaluated in the dose escalation
stage of a Phase 1 clinical trial in patients with unresectable
PDGFRα-driven GIST and patients with treatment-resistant KIT-driven
GIST. As of the data cutoff date of November
1, 2016, 36 patients had been treated in the dose escalation
portion of the Phase 1 clinical trial at seven dose levels (ranging
from 30 mg once daily (QD) to 400 mg QD), including 18 patients
with PDGFRα-driven GIST and 18 patients with KIT-driven GIST. The
median age was 61 (ranging from 41 to 77), and the median number of
prior tyrosine-kinase inhibitor (TKI) regimens was 3.5 (ranging
from zero to 12).
Preliminary pharmacokinetic analysis demonstrated relatively
rapid absorption of BLU-285 and a mean half-life of over 24 hours
that supports once daily dosing.
Preliminary Safety Data
As of the data cutoff date of November 1,
2016, BLU-285 was observed to be well-tolerated at all
doses. The majority of adverse events (AEs) reported by
investigators were Grade 1 or 2. Across all grades, AEs reported by
investigators most commonly included nausea (42%), vomiting (33%),
peripheral edema (31%), fatigue (28%) and constipation (22%).
Investigators reported treatment-related Grade 3 AEs in three
patients: nausea and vomiting (one patient); anemia and
intratumoral hemorrhage (one patient); and hypophosphatemia (one
patient). No dose-limiting toxicities or drug-related Grade 4 or 5
AEs were reported, and no patients discontinued BLU-285 due to
treatment-related adverse events. A maximum tolerated dose (MTD)
has not been reached, and enrollment in the dose escalation portion
of the Phase 1 clinical trial is ongoing.
Preliminary Clinical Activity Data
As of the data cutoff date of November 1,
2016, 28 patients in the first six cohorts of the dose
escalation portion of the clinical trial (at doses ranging from 30
mg QD to 300 mg QD) had completed at least two 28-day dosing cycles
and were evaluable for response assessment. CT and MRI imaging was
used to measure clinical activity by Response Evaluation Criteria
In Solid Tumors (RECIST) version 1.1.
- In PDGFRα-driven GIST, investigators observed radiographic
tumor reduction in 14 of 15 evaluable patients with six patients
achieving a partial response (PR) by RECIST (five confirmed, one
unconfirmed). Tumor reduction was observed at the first dose level
in the PDGFRα-driven subgroup of advanced GIST.
- In KIT-driven GIST, investigators observed radiographic tumor
reduction in five of the 13 evaluable patients, including one who
achieved a PR by RECIST (confirmed). At the higher dose levels
(greater than or equal to 135 mg), four out of six patients had
tumor reduction, including the patient with a PR, suggesting
increased clinical activity with increased dose. Tumor shrinkage
was first observed at the fourth dose level in the KIT-driven
subgroup of advanced GIST.
- Among all 36 patients treated, 27 patients remained on BLU-285,
including all 18 patients with PDGFRα-driven GIST, with a duration
of treatment ranging from 0.8 months to 12.3 months.
- Nine patients discontinued treatment with BLU-285 due to
progressive disease.
Clinical Development Plans for BLU-285 in GIST
Based on the favorable safety profile and encouraging clinical
activity observed to date in the Phase 1 clinical trial for BLU-285
for the treatment of advanced GIST, Blueprint Medicines will
continue to enroll patients in the dose escalation portion of this
clinical trial until a MTD or a lower recommended dose for further
clinical evaluation has been established. Enrollment in the
expansion cohorts for this Phase 1 clinical trial is expected to
begin in the first half of 2017. Blueprint Medicines plans to
enroll approximately 35 patients with advanced GIST in the
expansion cohorts. We also plan to accelerate our evaluation of
expanded development options for BLU-285 in GIST, including
opportunities to move to earlier lines of therapy and possible
combinations.
In January 2016, the U.S. Food and
Drug Administration (FDA) granted orphan drug designation to
BLU-285 for the treatment of GIST, and in October 2016, the FDA granted Fast Track
designation to BLU-285 for the treatment of patients with
unresectable or metastatic GIST that progressed following treatment
with imatinib and a second TKI and for the treatment of patients
with unresectable or metastatic GIST with the PDGFRα D842V mutation
regardless of prior therapy. Blueprint Medicines plans to seek
regulatory guidance on potential pathways for expedited clinical
development of BLU-285 for the treatment of advanced GIST.
Conference Call Information
Blueprint Medicines will host a conference call and webcast on
Thursday, December 1, 2016 at
12:30 p.m. ET (6:30 p.m. CET) to discuss the preliminary
clinical data for BLU-285 in GIST. The data will be presented on
December 1, 2016 by Michael Heinrich, M.D., Oregon Health &
Science University, in an oral presentation, "Preliminary Safety
and Activity in a First-in-Human Phase 1 Study of BLU-285, a
Potent, Highly-Selective Inhibitor of KIT and PDGFRα Activation
Loop Mutants in Advanced Gastrointestinal Stromal Tumor (GIST),"
(Abstract 6LBA) at the 28th EORTC-NCI-AACR Symposium on Molecular
Targets and Cancer Therapeutics in Munich, Germany at 4:00
p.m. CET (10:00 a.m. ET). As
part of the conference call and webcast, Blueprint Medicines will
also be discussing the preliminary data from the dose escalation
portion of its Phase 1 clinical trial for BLU-554, an
investigational medicine in development for patients with advanced
hepatocellular carcinoma, which was presented in a poster
presentation at EORTC-NCI-AACR.
To participate in the conference call, please dial
1-855-728-4793 (domestic) or 1-503-343-6666 (international) and
refer to conference ID 10770449. A live webcast of the presentation
will also be available under "Events and Presentations" in the
Investors section of Blueprint Medicines' website at
http://ir.blueprintmedicines.com. A replay of the webcast will be
available approximately two hours after the conference call and
will be available for 30 days following the call.
About the Phase 1 Clinical Trial for BLU-285 for
PDGFRα-Driven and KIT-Driven GIST
Blueprint Medicines' Phase 1 clinical trial for BLU-285 for the
treatment of patients with unresectable PDGFRα-driven GIST and
treatment-resistant KIT-driven GIST is designed to evaluate the
safety and tolerability of BLU-285 in multiple ascending doses with
the goal of establishing an MTD or a lower recommended dose. All
patients are tested retrospectively for both PDGFRα D842 and KIT
mutational status. Once the MTD is reached, or a recommended dose
is established, Blueprint Medicines plans to open expansion cohorts
for patients with a PDGFRα D842 mutation, regardless of line of
therapy, and for patients who have received imatinib and at least
one other KIT-directed TKI, clinically selecting for patients with
KIT-driven GIST who have a KIT Exon 17 mutation. Secondary
objectives include assessing response rate by RECIST version 1.1
criteria commonly used to measure clinical responses in solid
tumors, the pharmacokinetics of BLU-285 and allelic burden using
circulating tumor DNA. The Phase 1 clinical trial is designed to
enroll approximately 60 patients, including approximately 25
patients during dose escalation and approximately 35 additional
patients in expansion cohorts, at multiple sites in the United States, European Union and
Asia. Please refer to
www.clinicaltrials.gov for additional details related to this Phase
1 clinical trial (NCT02508532). For more information, please
contact the study director for this Phase 1 clinical trial at
studydirector@blueprintmedicines.com.
About GIST
GIST is the most common sarcoma, or tumor of bone or connective
tissue, of the gastrointestinal (GI) tract. Tumors arise from
cells in the wall of the GI tract and occur most often in the
stomach or small intestine. Most patients are diagnosed
between the ages of 50-80, and diagnosis is
typically triggered by GI bleeding, incidental findings during
surgery or imaging and, in rare cases, tumor rupture or GI
obstruction. Approximately 80 percent of GIST patients have
KIT-driven GIST, and Blueprint Medicines estimates that KIT Exon 17
mutations occur in approximately 90 percent of GIST patients with
KIT-driven GIST following treatment with at least two TKIs.
Approximately five percent of all advanced GIST cases are driven by
D842V mutant PDGFRα. Patients diagnosed with GIST at an early
stage may undergo surgery. For patients with KIT-driven GIST,
treatment with the currently approved frontline therapy typically
leads to treatment resistance and disease progression. Treatment
options for KIT-driven GIST patients whose disease progresses or
develops resistance are currently limited, with approved therapies
providing a progression free survival of up to six months and a
response rate between five percent and seven percent. There are no
effective treatment options for patients with PDGFRα-driven GIST,
and progression can occur in as little as three months with
available treatment options.
About BLU-285
BLU-285 is an orally available, potent and highly selective
inhibitor of D842V mutant PDGFRα and Exon 17 mutant KIT. Blueprint
Medicines is initially developing BLU-285, an investigational
medicine, for the treatment of patients with advanced GIST and
advanced systemic mastocytosis. BLU-285 was discovered by Blueprint
Medicines' research team leveraging its proprietary compound
library, and Blueprint Medicines retains worldwide development and
commercialization rights for BLU-285.
About Blueprint Medicines
Blueprint Medicines is developing a new generation of
targeted kinase medicines to improve the lives of patients with
genomically defined diseases. Its approach is rooted in a deep
understanding of the genetic blueprint of cancer and other diseases
driven by the abnormal activation of kinases. Blueprint
Medicines is advancing three programs in clinical development
for subsets of patients with gastrointestinal stromal tumors,
hepatocellular carcinoma and systemic mastocytosis, as well as
multiple programs in research and preclinical development.
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 plans and timelines for the clinical development of
BLU-285; our ability to implement our clinical development plans
for BLU-285 for the treatment of advanced GIST; our ability to
enroll patients in our ongoing Phase 1 clinical trial for BLU-285
in advanced GIST; and Blueprint Medicines' strategy, business plans
and focus. 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 trials or the development of Blueprint
Medicines' drug product candidates, including BLU-285 and BLU-554;
Blueprint Medicines' advancement of multiple early-stage efforts;
Blueprint Medicines' ability to successfully demonstrate the
efficacy and safety of its drug product candidates; the preclinical
and clinical results for Blueprint Medicines' drug product
candidates, which may not support further development of such drug
product candidates; and actions of regulatory agencies, which may
affect the initiation, timing and progress of clinical trials;
Blueprint Medicines' ability to develop and commercialize companion
diagnostics for its current and future drug candidates, including
companion diagnostics for BLU-554 with Ventana Medical Systems,
Inc. and for BLU-285 with QIAGEN Manchester Limited; and the
success of Blueprint Medicines' rare genetic disease collaboration
with Alexion Pharma Holding and its cancer immunotherapy
collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche
Inc. These and other risks and uncertainties are described in
greater detail in the section entitled "Risk Factors" in Blueprint
Medicines' Quarterly Report on Form 10-Q for the quarter ended
September 30, 2016, as filed with the
Securities and Exchange Commission (SEC) on November 10, 2016, and other filings that
Blueprint Medicines may make with the SEC in the future. Any
forward-looking statements contained in this press release
represent Blueprint Medicines' views only as of the date hereof and
should not be relied upon as representing its views as of any
subsequent date. Blueprint Medicines explicitly disclaims any
obligation to update any forward-looking statements.
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