-- Updated Phase 1 dose escalation data show
that BLU-222 in combination with ribociclib and fulvestrant was
well-tolerated at clinically active dose levels with no
dose-limiting toxicities --
-- Early signal of clinical activity includes
compelling biomarker reductions correlated with BLU-222 exposure
--
CAMBRIDGE, Mass., May 23, 2024
/PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC)
today announced updated data from the ongoing Phase 1 dose
escalation portion of the VELA clinical trial of BLU-222, an
investigational, highly selective and potent CDK2 inhibitor, in
combination with ribociclib and fulvestrant in patients with
hormone-receptor-positive/human epidermal growth factor receptor
2-negative (HR+/HER2-) breast cancer. The data, which mark the
first promising clinical results for a CDK2 inhibitor in
combination with an approved CDK4/6 inhibitor, will be presented at
the 2024 American Society of Clinical Oncology (ASCO) Annual
Meeting on June 2, 2024.
"At ASCO, we will present highly encouraging clinical data
showing that our selective CDK2 inhibitor BLU-222, in combination
with ribociclib, a standard of care CDK4/6 inhibitor for HR+ breast
cancer, is very well-tolerated and delivers early evidence of
clinical activity. This represents a highly significant milestone
and holds promise as an important new cornerstone for the treatment
of breast cancer, including in the front-line metastatic setting,"
said Becker Hewes, M.D., Chief Medical Officer at Blueprint
Medicines. "These data validate the potency and selectivity of
BLU-222, its potential as a first- and best-in-class CDK2
inhibitor, and its use as the combination partner of choice in
breast cancer. With these data in hand, we are advancing ongoing
partnering discussions that aim to accelerate development of
BLU-222 into registration-directed clinical trials."
Updated Phase 1/2 VELA Trial Results
Based on previously reported positive BLU-222 monotherapy
clinical data, a combination dose escalation arm was initiated in
the VELA trial to assess the safety and clinical activity of
BLU-222 in combination with ribociclib, a CDK4/6 inhibitor approved
by the U.S. Food and Drug Administration for advanced or metastatic
HR+/HER2- breast cancer, and fulvestrant, a commonly used estrogen
receptor antagonist. As of the data cutoff date, 19 patients with
HR+/HER2- breast cancer who had progressed on prior CDK4/6
inhibitors were treated with 100 mg to 400 mg twice daily (BID) of
BLU-222 plus 400 mg once daily (QD) of ribociclib and combined with
fulvestrant.
The combination of BLU-222, ribociclib, and fulvestrant was
well-tolerated at all BLU-222 dose levels tested. No dose-limiting
toxicities, treatment-related severe adverse events (SAEs), or
BLU-222-related treatment discontinuations were reported.
Treatment-related hematologic and gastrointestinal AEs were
generally mild. The maximum tolerated combination dose has not been
identified, and combination dose escalation is ongoing.
Pharmacokinetic data showed dose-proportional exposures of
BLU-222, with sustained coverage above the predicted efficacious
concentration at the 400 mg BID dose level. In addition, the
combination of BLU-222 with ribociclib and fulvestrant had no
clinically meaningful impact on individual drug exposures.
Preliminary clinical activity showed compelling reductions in
thymidine kinase 1 (TK1) and circulating tumor DNA (ctDNA),
biomarkers that have been shown to be predictive of clinical
benefit. TK1, a biomarker of tumor proliferation, had the deepest
reduction among patients treated with BLU-222 400 mg BID,
ribociclib 400 mg QD, and combined with fulvestrant, and was
statistically significantly correlated with BLU-222 exposure. All
patients with evaluable ctDNA, a biomarker of tumor burden,
treated with the BLU-222 400 mg BID combination dose regimen showed
ctDNA reductions. Early evidence of clinical benefit includes an
unconfirmed partial response in a patient who had previously
progressed following six lines of therapy in the metastatic
setting, including prior palbociclib and trastuzumab deruxtecan.
These data highlight the impact of CDK2 inhibition when BLU-222 is
combined with other therapies.
Detailed data will be presented by Dr. Dejan Duric from the Henri and Belinda Termeer
Center for Targeted Therapies at Massachusetts General Hospital on
June 2, 2024, during the "Breast
Cancer – Metastatic" poster session at 9:00
a.m. CT. At the time of presentation, a copy of the poster
will be available in the "Science—Publications and Presentations"
section of the company's website at www.BlueprintMedicines.com.
About BLU-222
BLU-222 is a highly selective and potent investigational CDK2
inhibitor with first- and best-in-class potential, designed by
scientists at Blueprint Medicines. CDK2 is a cell cycle regulator
and an important cancer target, with relevance in HR+/HER2- breast
cancer and other malignancies, such as subsets of ovarian and
endometrial cancer. Across multiple cancer types, aberrant CCNE1
hyperactivates CDK2, resulting in cell cycle dysregulation and
tumor proliferation. Aberrant CCNE1 has been observed as a primary
driver of disease, as well as a mechanism of resistance to CDK4/6
inhibitors. In HR+/HER2- breast cancer, the advent of CDK4/6
inhibitors has improved treatment; however, disease progression is
nearly universal, and new innovation is needed to improve outcomes
and prolong clinical benefit. Historically, CDK2 inhibitor
development by others has been challenged due to poor selectivity
limiting tolerability and combination potential. Beyond BLU-222,
Blueprint Medicines is advancing additional preclinical therapeutic
candidates for cell cycle targets including BLU-956, a
next-generation CDK2 inhibitor, a CDK2 targeted protein degradation
program, and an additional undisclosed research program.
About Blueprint Medicines
Blueprint Medicines is a global, fully integrated
biopharmaceutical company that invents life-changing medicines. We
seek to alleviate human suffering by solving important medical
problems in two core focus areas: allergy/inflammation and
oncology/hematology. Our approach begins by targeting the root
causes of disease, using deep scientific knowledge in our core
focus areas and drug discovery expertise across multiple
therapeutic modalities. We have a track record of success with two
approved medicines, including
AYVAKIT®/AYVAKYT® (avapritinib) which we are
bringing to patients with systemic mastocytosis (SM) in the U.S.
and Europe. Leveraging our
established research, development, and commercial capability and
infrastructure, we now aim to significantly scale our impact by
advancing a broad pipeline of programs ranging from early science
to advanced clinical trials in mast cell diseases including SM and
chronic urticaria, breast cancer and other solid tumors. For more
information, visit www.BlueprintMedicines.com and follow us on X
(formerly 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: statements
regarding plans, strategies, timelines and expectations for
Blueprint Medicines' operations, including its expectations for our
current or future approved drugs and drug candidates, including
BLU-222; the development of BLU-222 and whether it has first-and
best-in-class potential; the potential benefits of any of our
current or future approved drugs or drug candidates in treating
patients, including the potential benefits of BLU-222 in
combination with ribociclib and fulvestrant in patients with
HR+/HER2- breast cancer; and the potential to partner with a third
party to accelerate development of BLU-222 into
registration-directed clinical trials. 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 delay of any current or planned
clinical trials or the development of the company's current or
future drug candidates; the company's 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
possibility that preclinical and clinical results for the company's
drug candidates may not support further development of such drug
candidates either as monotherapies or in combination with other
agents or may impact the anticipated timing of data or regulatory
submissions; the timing of the initiation of clinical trials and
trial cohorts at clinical trial sites and the possibility patient
enrollment rates may be delayed or slower than anticipated; the
actions of regulatory agencies and how this may affect the
initiation, timing and progress of clinical trials; the company's
ability to obtain, maintain and enforce patent and other
intellectual property protection for its products and current or
future drug candidates it is developing; and the success of the
company's current and future collaborations, partnerships or
licensing arrangements. Any forward-looking statements contained in
this press release represent the company's 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, the company
explicitly disclaims any obligation to update any forward-looking
statements contained in this press release as a result of new
information, future events or otherwise. Accordingly, readers are
cautioned not to place undue reliance on these forward-looking
statements.
Trademarks
Blueprint Medicines and associated logos are trademarks of
Blueprint Medicines Corporation.
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