CAMBRIDGE, Mass., April 15, 2018 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ:BPMC), a leader in discovering
and developing targeted kinase medicines for patients with
genomically defined diseases, today announced proof-of-concept data
from the ongoing Phase 1 ARROW clinical trial of BLU-667 in
patients with RET-altered solid tumors. Designed and developed by
Blueprint Medicines, BLU-667 is a potent and highly selective
inhibitor targeting oncogenic RET fusions and mutations, which are
key drivers across multiple cancers, including subsets of patients
with non-small cell lung cancer (NSCLC) and medullary thyroid
cancer (MTC). The data will be presented today in a clinical
trials plenary session at the American Association for Cancer
Research (AACR) Annual Meeting in Chicago, Illinois.
The data from the dose escalation portion of the ARROW trial
showed broad and robust clinical activity for once-daily (QD)
dosing of BLU-667 across multiple tumor types and RET genotypes,
including in patients whose disease had progressed on prior
multi-kinase inhibitor therapy. As of the data cutoff date of
April 6, 2018, the data showed
radiographic tumor reductions in 84 percent of patients with
RET-altered solid tumors with measurable target lesions. In
patients evaluable for response, preliminary overall response rates
(ORR) were 50 percent in patients with NSCLC and 40 percent in
patients with MTC. As of the data cutoff date, QD dosing of BLU-667
was well-tolerated, and most adverse events (AEs) reported by
investigators were Grade 1 or 2.
"The data announced today reveal the broad clinical potential of
BLU-667, a potent and highly selective RET inhibitor, and further
demonstrate the power and reproducibility of Blueprint Medicines'
proprietary drug discovery platform," said Andy Boral, M.D., Ph.D., Chief Medical Officer
at Blueprint Medicines. "We believe the safety, clinical activity
and pharmacodynamic results from the dose escalation portion of the
Phase 1 ARROW trial demonstrate compelling proof-of-concept for
BLU-667. We are particularly encouraged by the consistency of these
early BLU-667 data across multiple tumor types, RET alterations and
prior lines of therapy. Based on these data, we are excited to
rapidly advance the global expansion portion of the trial, which
will further evaluate an optimized dose of BLU-667 across a broad
patient population with a focus on durability of activity."
Data from the Ongoing Phase 1 ARROW Clinical Trial
As of the data cutoff date of April 6,
2018, 53 patients had been treated with BLU-667 in the dose
escalation portion of the Phase 1 ARROW clinical trial across
multiple dose levels ranging from 30 mg to 600 mg QD, including 19
patients with NSCLC, 29 patients with MTC and five patients with
other solid tumors. Of these 53 patients, 27 patients (51 percent)
had been previously treated with a multi-kinase inhibitor and 18
patients (34 percent) had been previously treated with an
immunotherapy.
Pharmacokinetic (PK) data across all QD dose levels demonstrated
rapid absorption of BLU-667 and a mean half-life greater than 12
hours, supporting a QD dosing regimen.
Preliminary Safety Data:
As of the data cutoff date, QD dosing of BLU-667 was observed to
be well-tolerated. The maximum tolerated dose (MTD) for BLU-667 was
determined to be 400 mg QD using a Bayesian optimal interval
design. At QD dose levels up to and including the MTD, the majority
of AEs reported by investigators were Grade 1 or 2. AEs reported by
investigators (≥20 percent) most commonly included constipation (24
percent), increased alanine aminotransferase (ALT) (22 percent) and
increased aspartate aminotransferase (20 percent). Investigators
reported treatment-related Grade 3 AEs in eight patients (16
percent). Treatment-related Grade 3 AEs occurring in two or more
patients included hypertension and neutropenia. There were no
treatment-related Grade 4 or 5 AEs.
Across all QD dose levels up to 600 mg QD, seven patients
experienced dose-limiting toxicities. Only one patient discontinued
treatment with BLU-667 due to a dose-limiting toxicity (Grade 3 ALT
increase). An additional 11 patients discontinued treatment,
including eight patients due to progressive disease, one patient
due to an AE unrelated to BLU-667 and one patient due to
non-compliance. One patient passed away, and the death was deemed
unrelated to BLU-667. Among all 53 enrolled patients, 41 patients
(77 percent) remained on BLU-667 as of the data cutoff date.
Duration of treatment ranged from 0.3 to 11.5 months.
Preliminary Clinical Activity Data:
As of the data cutoff date, 40 patients with RET-altered tumors
were evaluable for response assessment, including 14 patients with
NSCLC, 25 patients with MTC and one patient with papillary thyroid
cancer (PTC). CT and MRI imaging was used to measure clinical
activity by Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1. Of the remaining 13 enrolled patients who were not
evaluable for response assessment, two patients did not have
RET-altered tumors, one patient died due to an AE unrelated to
BLU-667 prior to any response assessment and 10 recently enrolled
patients had not been evaluated for response by the data cutoff
date.
Across all evaluable patients, the preliminary ORR was 45
percent. Responses were observed in patients previously treated
with multi-kinase therapy, immunotherapy and chemotherapy.
RET-altered NSCLC
- 85% of NSCLC patients with measurable target lesions had
radiographic tumor reductions.
- Seven patients achieved a partial response (PR) (five
confirmed, two pending confirmation), representing a preliminary
ORR of 50 percent.
- Responses were observed in patients with the most common RET
alterations in NSCLC, including RET-KIF5B and RET-CCDC6
fusions.
- Preliminary evidence of anti-tumor activity in the brain was
observed in metastatic NSCLC.
RET-altered MTC
- 83% of MTC patients with measurable target lesions had
radiographic tumor reductions.
- One patient achieved a confirmed complete response, nine
patients achieved a PR (five confirmed, four pending confirmation),
representing a preliminary ORR of 40 percent.
- Responses were observed in patients with the most common
activating RET mutations in MTC, including the RET-M918T
mutation.
Other RET-altered solid tumors
- One patient with RET-altered PTC achieved a PR (pending
confirmation).
Based on the favorable tolerability and encouraging clinical
activity observed for BLU-667 to date, Blueprint Medicines
initiated and is actively enrolling patients in the global
expansion portion of the ARROW trial.
Investor Event and Webcast Information
Blueprint Medicines will host an investor event on Sunday, April 15, 2018 beginning at 7:00 p.m. CT (8:00 p.m.
ET) in Chicago to review
the preliminary clinical data presented at AACR for BLU-667. Formal
presentations and the live webcast will begin at 7:30 p.m. CT (8:30 p.m.
ET). The event can be accessed by dialing 1-855-728-4793
(domestic) or 1-503-343-6666 (international) and providing the
passcode 6080608. A live webcast will also be available under
"Events & Presentations" in the Investors section
of Blueprint Medicines' website at
http://ir.blueprintmedicines.com. The archived webcast will
be available on Blueprint Medicines' website
approximately two hours after the event concludes and will be
available for 30 days following the event.
About the Phase 1 ARROW Clinical Trial of BLU-667
ARROW is a Phase 1 clinical trial of BLU-667 designed to
evaluate the safety and tolerability of BLU-667 in multiple
ascending doses in adults with RET-altered NSCLC, MTC and other
advanced solid tumors. The trial consists of two parts: a dose
escalation portion and an expansion portion. Enrollment in the dose
escalation portion is complete, and the expansion portion has been
initiated and is actively enrolling patients in four defined
cohorts at the MTD of 400mg QD: (1) RET-altered NSCLC patients
previously treated with a tyrosine kinase inhibitor (TKI), (2)
RET-altered NSCLC patients who have not previously received any TKI
treatment, (3) patients with medullary thyroid cancer, and (4)
patients with other RET-altered solid tumors. Trial objectives
include assessing response, pharmacokinetics, pharmacodynamics and
safety.
Patients and physicians interested in the ARROW trial can
contact the Blueprint Medicines study team at
studydirector@blueprintmedicines.com or 1-617-714-6707. More
information about the ARROW trial is also available at
www.arrowtrial.com or www.clinicaltrials.gov (Identifier:
NCT03037385).
About RET-Altered NSCLC, MTC and Other Solid Tumors
RET activating fusions and mutations are a key disease driver in
multiple cancers, including NSCLC and MTC. RET fusions are
implicated in approximately 1-2% of patients with NSCLC, while RET
mutations are implicated in approximately 60% of patients with MTC.
In addition, genomic analyses published by scientists
at Blueprint Medicines have identified RET fusions at low
frequencies in colon and breast cancer. 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.
About BLU-667
BLU-667 is an orally available, potent and highly selective
inhibitor designed to target RET fusions, mutations and predicted
resistance mutations. Blueprint Medicines is developing BLU-667, an
investigational medicine, for the treatment of patients with
RET-altered NSCLC, MTC and other solid tumors. BLU-667 was
discovered by Blueprint Medicine's research team leveraging its
proprietary compound library, and Blueprint Medicines retains
worldwide development and commercialization rights for BLU-667.
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 and timelines for advancing the expansion
portion of the Phase 1 ARROW trial; expectations regarding the
safety and efficacy of BLU-667 and the potential benefits of
BLU-667 in treating patients with RET-altered cancers; plans to
advance a QD dosing regimen for BLU-667; plans and timelines for
activating additional clinical sites in the Phase 1 ARROW trial;
expectations regarding enrollment in the expansion portion of the
Phase 1 ARROW trial; 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; and 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
HCC, avapritinib for PDGFRα D842V-driven GIST and BLU-667 for
RET-driven NSCLC; and the success of Blueprint Medicines' 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' Annual Report on Form 10-K for the year
ended December 31, 2017, as filed
with the Securities and Exchange Commission (SEC) on February 21, 2018, and 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. Blueprint Medicines explicitly disclaims
any obligation to update any forward-looking statements.
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