CAMBRIDGE, Mass., Sept. 26, 2018 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a leader in discovering and
developing targeted kinase medicines for patients with genomically
defined diseases, today announced the presentation and publication
of two clinical cases demonstrating proof-of-concept for BLU-667 in
combination with osimertinib (Tagrisso®) in treatment-resistant,
EGFR-mutant non-small cell lung cancer (NSCLC). In both cases, the
combined agents overcame resistance to standard treatment due to an
acquired RET fusion, resulting in significant tumor reductions. The
data are being presented today in a late-breaking oral presentation
at the International Association for the Study of Lung Cancer 19th
World Conference on Lung Cancer (WCLC) and published online in
Cancer Discovery.
"The combination of two highly selective agents ― BLU-667 and
osimertinib ― has the potential to become an important new tool to
overcome treatment resistance in a subset of patients with
EGFR-mutant, non-small cell lung cancer," said Lecia V. Sequist, M.D., Ph.D., medical
oncologist, Massachusetts General Hospital Cancer Center and
Associate Professor of Medicine, Harvard
Medical School, and senior author of the oral presentation
and paper. "We found that two pre-treated patients with advanced
disease, who acquired RET fusions resulting in resistance to
standard therapy, each showed a meaningful response only eight
weeks after initiating the combination regimen. These results are
highly encouraging and support further study of BLU-667 in
combination with osimertinib in additional patients."
BLU-667 is an investigational precision therapy designed to
potently and selectively inhibit RET alterations including
resistance mutations. It is currently being evaluated in the global
Phase 1 ARROW clinical trial in patients with RET-altered NSCLC,
medullary thyroid cancer (MTC) and other solid tumors.
Data Highlights
The WCLC presentation and Cancer
Discovery article included preclinical data and two clinical
cases highlighting the potential of combining BLU-667 and
osimertinib to overcome treatment resistance in EGFR-mutant
NSCLC.
The clinical cases included two patients treated with BLU-667
and osimertinib under investigator-sponsored protocols. The
patients had advanced EGFR-mutant NSCLC that progressed on standard
targeted therapy, with an acquired RET fusion identified via lung
biopsy. Radiographic scans after eight weeks showed both patients
experienced a partial response (both pending confirmation), with
each achieving a 78 percent reduction in target tumors per Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The
combination was well tolerated, and all reported adverse events
were Grade 1 or 2. Both patients continue to receive treatment as
of September 26, 2018.
Based on these data, Blueprint Medicines plans to explore
opportunities to evaluate the combination of BLU-667 and
osimertinib in additional patients with treatment-resistant,
EGFR-mutant NSCLC harboring a RET fusion.
The paper, titled, "Landscape of acquired resistance to
osimertinib in EGFR-mutant NSCLC and clinical validation of
combined EGFR and RET inhibition with osimertinib and BLU-667 for
acquired RET fusion," will be published online in Cancer
Discovery at 1:30 p.m. ET
on September 26, 2018.
About RET-Altered Solid Tumors
RET activating fusions
and mutations are a key disease driver in many cancer types,
including NSCLC and MTC. RET fusions are implicated in
approximately 1 to 2 percent of patients with NSCLC, while RET
mutations are implicated in approximately 60 percent of patients
with MTC. In addition, oncogenic RET alterations are observed at
low frequencies in colorectal, breast, pancreatic and other
cancers, and RET fusions have been observed in patients with
treatment-resistant, EGFR-mutant NSCLC.
Currently, there are no approved therapies that selectively
target RET-driven cancers, though there are several approved
multi-kinase inhibitors with RET activity being evaluated in
clinical trials. Thus far, clinical activity attributable to
RET inhibition has been uncertain for these inhibitors, likely due
to insufficient inhibition of RET and off-target toxicities. There
is a need for precision therapies that provide durable clinical
benefit by selectively targeting RET alterations and resistance
mutations.
About BLU-667
BLU-667 is an investigational,
once-daily oral precision therapy specifically designed for highly
potent and selective targeting of oncogenic RET fusions, mutations
and resistance mutations. In preclinical studies, BLU-667
consistently demonstrated sub-nanomolar potency against the most
common RET fusions, activating mutations and resistance mutations.
In addition, BLU-667 demonstrated markedly improved selectivity for
RET compared to approved multi-kinase inhibitors, including more
than 80-fold improved potency for RET versus VEGFR2. By suppressing
primary and secondary mutants, BLU-667 has the potential to
overcome and prevent the emergence of clinical resistance. This
approach is expected to enable durable clinical responses across
the range of RET alterations, with a favorable safety profile.
In April 2018, Blueprint Medicines
presented proof-of-concept data from its ongoing Phase 1 ARROW
clinical trial of BLU-667 in patients with RET-altered NSCLC, MTC
and other advanced solid tumors at the American Association for
Cancer Research (AACR) Annual Meeting. The data showed broad and
robust clinical activity across multiple tumor types and RET
genotypes, including in patients whose disease had progressed on
prior multi-kinase therapy. Radiographic tumor reductions were
observed in 84 percent of patients with RET-altered solid tumors
and measurable target lesions. The data also showed that BLU-667
was generally well-tolerated, and most adverse events reported by
investigators were Grade 1. Global enrollment in the dose expansion
portion of the Phase 1 ARROW clinical trial is ongoing.
Patients and physicians interested in the ARROW clinical trial
can contact the Blueprint Medicines study director at
arrow@blueprintmedicines.com or 1-617-714-6707. Additional details
are also available at www.arrowtrial.com or www.clinicaltrials.gov
(ClinicalTrials.gov Identifier: NCT03037385).
BLU-667 was discovered by Blueprint Medicine's research team
based on its proprietary compound library. The company is
developing BLU-667 for the treatment of people with RET-altered
NSCLC, MTC and other solid tumors. Blueprint Medicines has an
exclusive collaboration and license agreement with CStone
Pharmaceuticals for the development and commercialization of
BLU-667 and certain other drug candidates in Mainland China,
Hong Kong, Macau and Taiwan. Blueprint Medicines retains
development and commercial rights for BLU-667 in the rest of the
world.
About Blueprint Medicines
Blueprint
Medicines is developing a new generation of targeted and
potent 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 disease
driven by the abnormal activation of kinases. Blueprint
Medicines is advancing multiple programs in clinical
development for subsets of patients with gastrointestinal stromal
tumors, hepatocellular carcinoma, systemic mastocytosis, non-small
cell lung cancer, medullary thyroid cancer and other advanced solid
tumors, as well as multiple programs in research and preclinical
development. For more information, please
visit www.blueprintmedicines.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,
statements regarding plans and timelines for the clinical
development of BLU-667, including plans to explore opportunities to
evaluate the combination of BLU-667 and osimertinib in additional
patients with treatment-resistant, EGFR-mutant NSCLC harboring a
RET fusion; expectations regarding the potential benefits of
BLU-667 in treating patients with RET-altered cancers, including
patients with treatment-resistant, EGFR-mutant NSCLC; expectations
regarding the potential benefits of treatment with BLU-667 in
combination with other therapies, including osimertinib; 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 candidates, including avapritinib, BLU-554, BLU-667
and BLU-782; Blueprint Medicines' advancement of multiple
early-stage efforts; Blueprint Medicines' ability to successfully
demonstrate the safety and efficacy of its drug candidates; the
preclinical and clinical results for Blueprint Medicines' drug
candidates, which may not support further development of such drug
candidates; actions of regulatory agencies, which may affect the
initiation, timing and progress of clinical trials; Blueprint
Medicines' ability to develop and commercialize companion
diagnostic tests for its current and future drug candidates,
including companion diagnostic tests for BLU-554 for FGFR4-driven
hepatocellular carcinoma, avapritinib for PDGFRα D842V-driven
gastrointestinal stromal tumors and advanced systemic mastocytosis
and BLU-667 for RET-driven non-small cell lung cancer; the success
of Blueprint Medicines' current and future collaborations,
including its cancer immunotherapy collaboration with F.
Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. and its
collaboration with CStone Pharmaceuticals. 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 June 30,
2018, as filed with the Securities and Exchange Commission
(SEC) on August 1, 2018, and any
other filings that Blueprint Medicines has made or 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. Except as required by law,
Blueprint Medicines explicitly disclaims any obligation to update
any forward-looking statements.
Tagrisso® is a registered trademark of AstraZeneca plc. All
other trademarks and trade names in this press release are the
property of Blueprint Medicines Corporation.
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