CAMBRIDGE, Mass., Oct. 6, 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 of updated data
from the ongoing Phase 1 ARROW clinical trial of BLU-667, an
investigational precision therapy targeting RET alterations,
including resistance mutations. The new results showed that BLU-667
was highly active and well-tolerated in patients with advanced
RET-altered medullary thyroid cancer (MTC) and papillary thyroid
cancer (PTC), with increased activity observed with higher dose
levels and longer treatment durations.
The reported data showed 90 percent of evaluable patients with
MTC and PTC had radiographic tumor reductions, regardless of RET
alteration type or prior multi-kinase inhibitor (MKI) therapy. In
addition, the response rate was 62 percent in patients with MTC
treated once daily (QD) with BLU-667 at doses of 300 to 400 mg for
at least 24 weeks. In the MTC and PTC populations, all responders
across dose levels and all patients treated at 400 mg QD remain on
study. Safety results were consistent with prior data, and the
majority of adverse events (AEs) were Grade 1. These results were
as of a data cutoff date of September 14,
2018 and were reported today in an oral presentation at The
88th Annual Meeting of the American Thyroid Association (ATA).
"Existing treatment of medullary and papillary thyroid cancer
with multi-kinase inhibitors is limited by frequent dose
modifications or interruptions due to off-target toxicities,
reducing the opportunity for a meaningful or sustained response,"
said Andy Boral, M.D., Ph.D., Chief
Medical Officer of Blueprint Medicines. "These new data showed
selectively targeting RET alterations with BLU-667 was
well-tolerated and enabled durable responses. Importantly, response
rates were high for patients with prolonged time on therapy at
higher dose levels, demonstrating that potent and sustained target
inhibition leads to improved patient outcomes. We believe these
results begin to reveal the potential of BLU-667 to transform the
care of patients with RET-altered thyroid cancer, and we look
forward to seeing the data continue to mature as additional
patients are treated at the recommended phase 2 dose for longer
durations."
Based on the encouraging data reported to date, Blueprint
Medicines has expanded enrollment targets for the ARROW trial to
further evaluate the safety and efficacy of BLU-667 in a broader
patient population and, ultimately, to support potential
registration.
Data Highlights from the Ongoing Phase 1 ARROW Clinical
Trial
The data presented included all patients enrolled in the Phase 1
ARROW clinical trial as of May 9,
2018 and included follow-up on these patients through the
data cutoff date of September 14,
2018. Of the 69 patients who had been treated with BLU-667
in the dose escalation and expansion portions of the trial, 42 had
RET-altered thyroid cancer, including 37 with MTC and five with
PTC. In the dose escalation portion, patients were treated at dose
levels ranging from 30 mg to 600 mg QD or up to 300 mg twice daily.
In the expansion portion, patients were treated at the recommended
phase 2 dose of 400 mg QD.
Clinical Activity Data
As of the data cutoff date, 35 patients with MTC and four
patients with PTC were evaluable for response assessment by
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Overall, 90 percent of MTC and PTC patients with measurable target
lesions had radiographic tumor reductions.
In patients with MTC, response assessments showed increased
clinical activity with higher dose levels and longer treatment
durations. Across all evaluable MTC patients, the overall response
rate (ORR) was 49 percent, including one patient with a confirmed
complete response (CR) and 16 patients with a partial response (PR;
two pending confirmation). In patients with MTC treated with 300 to
400 mg QD for at least 24 weeks, the response rate was 62 percent,
including one patient with a confirmed CR and seven patients with a
confirmed PR.
In patients with PTC, two of four evaluable patients had a
confirmed PR, and all evaluable patients with PTC had radiographic
tumor shrinkage.
The data also showed encouraging evidence of durable activity.
All patients with MTC and PTC who responded to BLU-667 remain on
treatment as of the data cutoff date. In addition, all patients
treated at 400 mg QD are continuing on therapy. Patients with the
longest treatment durations remain on therapy for more than 15
months.
Anti-tumor activity was observed regardless of prior MKI therapy
or RET alteration. Similar response rates were observed in MTC
patients who were MKI-experienced (47 percent; 8/17 patients) and
MKI-naïve (50 percent; 9/18 patients). In addition, clinical
responses were observed in patients with common activating
mutations in MTC (e.g., M918T) and fusion partners in PTC (e.g.,
NCO4A and CCDC6). A clinical response was also observed in the one
evaluable MTC patient with a germline V804M gatekeeper
mutation.
Safety Data
The reported data showed that across 69 patients, BLU-667 was
well-tolerated as of the data cutoff date. Most AEs were Grade 1,
and only two patients discontinued therapy due to a
treatment-related AE (Grade 3 increased alanine aminotransferase in
a patient with liver metastases and Grade 2 pneumonitis).
Treatment-emergent AEs (regardless of relationship to BLU-667)
reported by investigators (≥15 percent) most commonly were
constipation (35 percent), increased aspartate aminotransferase (33
percent), anemia (30 percent), hypertension (30 percent), decreased
white blood cell count (29 percent), diarrhea (28 percent),
neutropenia (28 percent), increased alanine aminotransferase (25
percent), increased blood creatinine (23 percent), fatigue (19
percent) and headache (17 percent). Grade 3 or higher
treatment-related AEs occurring in two or more patients included
anemia, hypertension, decreased white blood cell count, diarrhea
and neutropenia.
About the Phase 1 ARROW Clinical Trial of BLU-667
ARROW is a Phase 1 clinical trial designed to evaluate the
safety, tolerability and efficacy of BLU-667 in multiple ascending
doses in adults with RET-altered non-small cell lung cancer
(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 six defined cohorts at the recommended phase 2 dose of
400 mg QD: (1) RET-altered NSCLC patients previously treated with
an MKI, (2) RET-altered NSCLC patients who have not previously
received any MKI treatment, (3) MTC patients previously treated
with an MKI, (4) MTC patients who have not previously received any
MKI treatment, (5) patients with other RET-altered solid tumors and
(6) RET-altered solid tumor patients with prior selective RET
tyrosine kinase inhibitor. Trial objectives include assessing
response, pharmacokinetics, pharmacodynamics and safety. The trial
is designed to enroll approximately 190 patients across all six
expansion cohorts, at multiple sites in the United States, European Union and
Asia.
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 available at www.arrowtrial.com or
www.clinicaltrials.gov (ClinicalTrials.gov Identifier:
NCT03037385).
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
and approximately 10 percent of patients with PTC, 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 MKIs
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 MKIs, 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.
BLU-667 was discovered by Blueprint Medicines' 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;
expectations regarding the potential benefits of BLU-667 in
treating patients with RET-altered thyroid cancers, including
patients with RET-altered MTC or PTC; expectations regarding the
potential to treat patients at the recommended phase 2 dose for
longer durations 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.
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