CAMBRIDGE, Mass., May 19, 2021 /PRNewswire/ -- Blueprint Medicines
Corporation (NASDAQ: BPMC) today announced the presentation of
updated Phase 1/2 ARROW trial data demonstrating durable clinical
benefits of GAVRETO® (pralsetinib) in metastatic RET
fusion-positive non-small cell lung cancer (NSCLC) and other
advanced solid tumors. GAVRETO showed high response rates in
treatment-naïve patients with RET fusion-positive NSCLC, clinical
activity across a number of RET fusion-positive tumor types and a
safety profile consistent with previously reported results. These
data will be presented during the 2021 American Society of Clinical
Oncology (ASCO) Annual Meeting, June
4-8.
"Precision therapies have significantly improved outcomes in
non-small cell lung cancer driven by actionable biomarkers, and
these pralsetinib data show the transformative impact of targeting
RET alterations in the front-line treatment setting," said
Giuseppe Curigliano, M.D., Ph.D.,
Associate Professor of Medical Oncology at the University of
Milano and the Head of the
Division of Early Drug Development at the European Institute of
Oncology, IRCCS, Italy. "In
treatment-naïve metastatic NSCLC, these results are particularly
encouraging, with many patients remaining in response. The data
highlight the critical importance of identifying RET alterations
before initiating treatment, so that more patients have the
opportunity to benefit from targeted therapy."
"Updated data in metastatic RET fusion-positive non-small cell
lung cancer underscore how GAVRETO may transform the standard of
care, including in the first-line treatment setting," said Becker
Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "The
results in treatment-naïve patients with RET fusion-positive NSCLC
reflect the compelling clinical profile of GAVRETO, with high
response rates and durability of response that have strengthened
over time. In other RET-altered cancers, target lesions were
reduced across a diverse range of tumor types, with the majority of
patients responding to treatment. In collaboration with Genentech,
we look forward to engaging with the FDA based on the strength of
these data in metastatic RET fusion-positive solid tumors."
Clinical Activity Data
The ASCO data included response-evaluable populations comprising
216 patients with RET fusion-positive NSCLC who had measurable
disease at baseline and received a starting GAVRETO dose of 400 mg
once daily, and 19 patients with other RET fusion-positive solid
tumors, as of a date cutoff date of November
6, 2020. Tumor response was assessed by blinded independent
central review using Response Evaluation Criteria in Solid Tumors
(RECIST) version 1.1, and all responses were confirmed.
RET Fusion-Positive NSCLC
With a median follow-up of 17.1 months, GAVRETO showed durable
clinical benefits in patients with RET fusion-positive NSCLC with
or without prior therapy. In 68 treatment-naïve patients, the
overall response rate (ORR) was 79 percent (95% CI: 68%, 88%). The
complete response (CR) rate was 6 percent, 10 percent of patients
had complete regression of target tumors, and 74 percent of
patients had a partial response (PR). The median duration of
response (DOR) was not reached (95% CI: 9.0 months, not
reached).
For treatment-naïve patients, the initial study protocol limited
enrollment to those determined by the investigator to be ineligible
for standard platinum-based chemotherapy, which may be due to age,
comorbidities or other poor prognostic factors. This eligibility
restriction was removed in July 2019,
with the goal of including a population more reflective of
real-world practice. In an exploratory analysis of treatment-naïve
patients enrolled after this expansion of inclusion criteria
(n=25), the ORR was 88 percent (95% CI: 69%, 98%), and all
responses were PRs.
In 126 patients who previously received platinum-based
chemotherapy, the ORR was 62 percent (95% CI: 53%, 70%). The CR
rate was 4 percent, 12 percent of patients had complete regression
of target tumors, and 58 percent of patients had a PR. The median
DOR was 22.3 months (95% CI: 15.1 months, not reached).
Other RET Fusion-Positive Solid Tumors
In a heavily pre-treated patient population who had a median
follow-up of 12.1 months, GAVRETO showed clinical activity across
multiple additional RET-driven tumor types. In 19 patients with a
variety of RET fusion-positive solid tumors beyond NSCLC and
thyroid cancer, the ORR was 53 percent (95% CI: 29%, 76%) and the
median DOR was 19.0 months (95% CI: 5.5 months, not estimable).
Tumor reductions were shown in patients with the following cancers
– pancreatic, cholangiocarcinoma, colon, lung (except NSCLC),
mesenchymal, salivary duct, sweat gland and thymus – as well as
patients diagnosed with cancers of unknown primary origin. In the
three patients with pancreatic cancer, a particularly
difficult-to-treat tumor type, there was one CR and two PRs.
Safety Data
As of a data cutoff date of November 6,
2020, a total of 471 patients were enrolled with a GAVRETO
dose starting at 400 mg once daily. Across tumor types, GAVRETO was
well-tolerated with no new safety signals observed. The most common
treatment-related adverse events (AEs) reported by investigators
(≥20 percent) were neutropenia, increased aspartate
aminotransferase (AST), anemia, decreased white blood cell count,
increased alanine aminotransferase (ALT), hypertension,
constipation and asthenia. Overall, 6 percent of patients
discontinued GAVRETO due to treatment-related AEs.
These updated data will be reported in two ASCO poster
presentations: one on RET fusion-positive NSCLC (Abstract #9089)
and one on RET fusion-positive solid tumors (Abstract #3079).
Copies of the data presentations will be available starting
June 4, 2021 in the
"Science―Publications and Presentations" section of Blueprint
Medicines' website.
About GAVRETO (pralsetinib)
GAVRETO (pralsetinib) is a once-daily oral targeted therapy
approved by the U.S. Food and Drug Administration (FDA) for the
treatment of three indications: adult patients with metastatic RET
fusion-positive NSCLC as detected by an FDA approved test, adult
and pediatric patients 12 years of age and older with advanced or
metastatic RET-mutant medullary thyroid cancer (MTC) who require
systemic therapy, and adults and pediatric patients 12 years of age
and older with advanced or metastatic RET fusion-positive thyroid
cancer who require systemic therapy and who are radioactive
iodine-refractory (if radioactive iodine is appropriate). These
indications are approved under accelerated approval based on ORR
and DOR. Continued approval for these indications may be contingent
upon verification and description of clinical benefit in
confirmatory trials. In addition, GAVRETO is approved by the
National Medical Products Administration (NMPA) of China for the treatment of adult patients with
locally advanced or metastatic RET fusion-positive NSCLC after
platinum-based chemotherapy.
GAVRETO is not approved for the treatment of any other
indication in the U.S. by the FDA or in China by the NMPA, or for any indication in
any other jurisdiction by any other health authority.
GAVRETO is designed to selectively and potently target oncogenic
RET alterations, including secondary RET mutations predicted to
drive resistance to treatment. In preclinical studies, GAVRETO
inhibited RET at lower concentrations than other pharmacologically
relevant kinases, including VEGFR2, FGFR2 and JAK2. For more
information, visit GAVRETO.com.
Blueprint Medicines and Roche are co-developing GAVRETO globally
(excluding Greater China) for the
treatment of patients with RET-altered NSCLC, various types of
thyroid cancer and other solid tumors. The European Medicines
Agency validated a marketing authorization application for GAVRETO
for the treatment of RET fusion-positive NSCLC. The FDA granted
breakthrough therapy designation to GAVRETO for the treatment of
RET fusion-positive NSCLC that has progressed following
platinum-based chemotherapy and for RET mutation-positive MTC that
requires systemic treatment and for which there are no acceptable
alternative treatments.
Blueprint Medicines has an exclusive collaboration and license
agreement with CStone Pharmaceuticals for the development and
commercialization of GAVRETO in Greater
China, which encompasses Mainland China, Hong Kong, Macau and Taiwan.
Enrollment is ongoing in the Phase 1/2 ARROW trial, including
for patients with various RET fusion-positive solid tumors, and in
the Phase 3 AcceleRET Lung trial for treatment-naïve patients with
RET fusion-positive NSCLC. For more information about GAVRETO
clinical trials, visit www.clinicaltrials.gov or
www.blueprintclinicaltrials.com.
About RET-Altered Solid Tumors
RET activating fusions and mutations are key disease drivers in
many cancer types, including NSCLC and multiple types of thyroid
cancer. RET fusions are implicated in approximately 1 to 2 percent
of patients with NSCLC and approximately 10 to 20 percent of
patients with papillary thyroid cancer, while RET mutations are
implicated in approximately 90 percent of patients with advanced
MTC. In addition, oncogenic RET fusions are observed at low
frequencies in colorectal, breast, pancreatic and other cancers, as
well as in patients with treatment-resistant EGFR-mutant NSCLC.
About Blueprint Medicines
Blueprint Medicines is a global precision therapy company that
invents life-changing medicines for people with cancer and
hematologic disorders. Applying an approach that is both precise
and agile, we create therapies that selectively target genetic
drivers, with the goal of staying one step ahead across stages of
disease. Since 2011, we have leveraged our research platform,
including expertise in molecular targeting and world-class drug
design capabilities, to rapidly and reproducibly translate science
into a broad pipeline of precision therapies. Today, we are
delivering our approved medicines to patients in the United States and Europe, and we are globally advancing multiple
programs for genomically defined cancers, systemic mastocytosis,
and cancer immunotherapy. For more information,
visit www.BlueprintMedicines.com and follow us
on Twitter (@BlueprintMeds) and LinkedIn.
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, plans, strategies,
timelines and expectations for Blueprint Medicines' current or
future approved drugs and drug candidates, including timelines for
regulatory interactions for GAVRETO for the treatment of
RET-altered cancers; the potential benefits of Blueprint Medicines'
current and future approved drugs or drug candidates in treating
patients; and Blueprint Medicines' strategy, goals and anticipated
milestones, business plans and focus. The words "aim," "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 impact of the COVID-19 pandemic to
Blueprint Medicines' business, operations, strategy, goals and
anticipated milestones, including Blueprint Medicines' ongoing and
planned research and discovery activities, ability to conduct
ongoing and planned clinical trials, clinical supply of current or
future drug candidates, commercial supply of current or future
approved products, and launching, marketing and selling current or
future approved products; Blueprint Medicines' ability and plans in
continuing to establish and expand a commercial infrastructure, and
successfully launching, marketing and selling current or future
approved products; Blueprint Medicines' ability to successfully
expand the approved indications for AYVAKIT™/AYVAKYT®
(avapritinib) and GAVRETO or obtain marketing approval for
AYVAKIT/AYVAKYT in additional geographies in the future; the delay
of any current or planned clinical trials or the development of
Blueprint Medicines' current or future drug candidates; Blueprint
Medicines' advancement of multiple early-stage efforts; Blueprint
Medicines' ability to successfully demonstrate the safety and
efficacy of its drug candidates and gain approval of its drug
candidates on a timely basis, if at all; 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 obtain, maintain and enforce patent and other
intellectual property protection for AYVAKIT/AYVAKYT, GAVRETO or
any drug candidates it is developing; Blueprint Medicines' ability
to develop and commercialize companion diagnostic tests for
AYVAKIT/AYVAKYT, GAVRETO or any of its current and future drug
candidates; and the success of Blueprint Medicines' current and
future collaborations, partnerships or licensing arrangements.
These and other risks and uncertainties are described in greater
detail in the section entitled "Risk Factors" in Blueprint
Medicines' filings with the Securities and Exchange Commission
(SEC), including Blueprint Medicines' most recent Annual Report on
Form 10-K, as supplemented by its most recent Quarterly Report on
Form 10-Q 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.
Trademarks
Blueprint Medicines, AYVAKIT/AYVAKYT, GAVRETO and associated
logos are trademarks of Blueprint Medicines Corporation.
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