Arm D of SEQUOIA study evaluated
treatment-naïve patients with high-risk chronic lymphocytic
leukemia or small lymphocytic lymphoma with del(17p) and/or TP53
mutation
Preliminary data suggest promising efficacy and
tolerability
Safety profile was consistent with results of
prior BRUKINSA studies
BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global
oncology company, announced the presentation of new data from the
SEQUOIA study of BRUKINSA® (zanubrutinib) today at the European
Hematology Association 2024 Hybrid Congress (EHA2024) in Madrid,
Spain in an oral session (Abstract S160). The presentation will
feature data from arm D of SEQUOIA evaluating BRUKINSA in
combination with venetoclax in treatment-naïve (TN) patients with
high-risk chronic lymphocytic leukemia (CLL) and/or small
lymphocytic lymphoma (SLL) with del(17p) and/or TP53 mutation. The
preliminary data demonstrate that in the 65 response-evaluable
patients treated with the combination, the overall response rate
(ORR) was 100%, and the rate of complete response (CR) plus CR with
incomplete hematopoietic recovery (CRi) was 48%. The safety profile
of the combination is consistent with that of the treatment
components, and no new safety signals were seen.
“Patients with untreated CLL with del(17p) or TP53 mutations
often face a poor prognosis, even in the front-line setting, so
there is a critical need to better understand how this patient
population responds to combination approaches,” said Alessandra
Tedeschi, M.D., Ph.D., consultant in hematology and Medical
Director of the Department of Hematology at the Niguarda Cancer
Center in Milan, Italy. “This arm of the SEQUOIA study showed that
zanubrutinib in combination with a BCL2 inhibitor demonstrates
promising efficacy and tolerability for high-risk CLL patients,
providing important information about the clinical profile of this
regimen.”
Overall, 66 patients with centrally assessed del(17p) and/or
TP53 mutation were enrolled in this arm of the SEQUOIA study.
Patients received BRUKINSA at 160 mg twice daily for three months,
followed by combination treatment of BRUKINSA at the same dose and
venetoclax with a ramp-up dosing to 400 mg once daily for 12 to 24
cycles until progressive disease, unacceptable toxicity or
confirmed undetectable minimal residual disease (MRD). In the 65
response-evaluable patients, ORR was 100%; the rate of CR+CRi was
48% (CR=46%; CRi=2%). Undetectable MRD was achieved in 59% of
patients in ≥1 peripheral blood sample and with a median study
follow up of 31.6 months. Median progression-free survival (PFS)
was not reached; 12- and 24-month PFS estimates were 95% and 94%,
respectively.
“SEQUOIA has shown that BRUKINSA is a highly effective
monotherapy treatment for TN CLL patients, including those with
high-risk markers like del(17p) and/or TP53 mutation. With one of
the largest pools of high-risk patients of any published study to
date, SEQUOIA arm D demonstrates how BCL2 inhibitor therapies can
complement BRUKINSA as a backbone therapy to achieve deep clinical
response even in this patient population,” said Mehrdad Mobasher,
M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “We
look forward to evaluating the potential for time-limited therapy
with longer follow-up and incorporating these findings into our
development program for our investigational next-generation BCL2
inhibitor sonrotoclax.”
The safety profile of BRUKINSA plus venetoclax was consistent
with results of prior studies of both medicines, and no new safety
signals were identified. In total, 97% of patients experienced ≥1
treatment emergent adverse effect (TEAE). The most common all-grade
non-hematologic TEAEs were infections (71%), COVID-19 (55%),
diarrhea (39%), nausea (30%) and contusion (29%). Grade ≥3
non-hematologic TEAEs occurred in 44% of patients; the most common
were infections (15%), diarrhea (9%), hypertension (8%) and second
primary malignancies (8%). The most common all grade and grade ≥3
hematologic toxicity was neutropenia (22% and 17%, respectively).
The proportion of patients at high risk for tumor lysis syndrome
(TLS) decreased 91% from 35% at screening to 3% after three cycles
of lead-in BRUKINSA, and no TLS was reported.
About SEQUOIA
SEQUOIA (NCT03336333) is a randomized, multicenter, global Phase
3 trial designed to evaluate the efficacy and safety of BRUKINSA in
patients with TN CLL or SLL. The trial consists of three
cohorts:
- Cohort 1 (n=479): randomized 1:1 to receive BRUKINSA (n=241) or
bendamustine plus rituximab (n=238) until disease progression or
unacceptable toxicity, in patients not harboring del(17p); data
from this group comprise the primary endpoint;
- Cohort 2 (n=110): patients with del(17p) receiving BRUKINSA as
a monotherapy; and
- Cohort 3/arm D (n=114): 66 patients with del(17p) and/or
pathogenic TP53 mutation received BRUKINSA in combination with
venetoclax. While patients without del(17p) (n=48) were later
included in this cohort, the data presented at EHA2024 do not
include these patients.
The results of Cohort 1 of the SEQUOIA study led to the
regulatory approval of zanubrutinib monotherapy in the treatment of
TN CLL in many countries across the world, including approvals by
the U.S. Food and Drug Administration and the European Medicines
Agency. Patients with del(17p) were not randomized in the Cohort 1
study, as these patients are known to experience poor clinical
outcomes and poor response to chemoimmunotherapy, the control arm
of the study. The primary endpoint of the trial is independent
review committee-assessed PFS. Secondary endpoints include
investigator-assessed PFS, IRC- and investigator-assessed ORR,
overall survival, PFS and ORR in patients with del(17p), and
safety. Results for Cohort 2 (arm C), representing high-risk
patients treated with BRUKINSA monotherapy, were presented at the
62nd ASH Annual Meeting in December 2020.1 This cohort of patients
with del(17p) achieved significant efficacy, with an 18-month PFS
of 90.6%, as assessed by investigator. Full study results were
published in Lancet Oncology.2
About BRUKINSA® (zanubrutinib)
BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine
kinase (BTK) designed to deliver complete and sustained inhibition
of the BTK protein by optimizing bioavailability, half-life, and
selectivity. With differentiated pharmacokinetics compared with
other approved BTK inhibitors, BRUKINSA has been demonstrated to
inhibit the proliferation of malignant B cells within a number of
disease-relevant tissues.
U.S. Indications and Important Safety Information for
BRUKINSA (zanubrutinib)
INDICATIONS
BRUKINSA is a kinase inhibitor indicated for the treatment of
adult patients with:
- Chronic lymphocytic leukemia (CLL) or small lymphocytic
lymphoma (SLL).
- Waldenstr�m’s macroglobulinemia (WM).
- Mantle cell lymphoma (MCL) who have received at least one prior
therapy.
- Relapsed or refractory marginal zone lymphoma (MZL) who have
received at least one anti-CD20-based regimen.
- Relapsed or refractory follicular lymphoma (FL), in combination
with obinutuzumab, after two or more lines of systemic
therapy.
The MCL, MZL and FL indications are approved under accelerated
approval based on overall response rate and durability of response.
Continued approval for these indications may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
IMPORTANT SAFETY
INFORMATION
Warnings and Precautions
Hemorrhage
Fatal and serious hemorrhage has occurred in patients with
hematological malignancies treated with BRUKINSA. Grade 3 or higher
hemorrhage including intracranial and gastrointestinal hemorrhage,
hematuria, and hemothorax was reported in 3.8% of patients treated
with BRUKINSA in clinical trials, with fatalities occurring in 0.2%
of patients. Bleeding of any grade, excluding purpura and
petechiae, occurred in 32% of patients.
Bleeding has occurred in patients with and without concomitant
antiplatelet or anticoagulation therapy. Coadministration of
BRUKINSA with antiplatelet or anticoagulant medications may further
increase the risk of hemorrhage.
Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA
if intracranial hemorrhage of any grade occurs. Consider the
benefit-risk of withholding BRUKINSA for 3-7 days before and after
surgery depending upon the type of surgery and the risk of
bleeding.
Infections
Fatal and serious infections (including bacterial, viral, or
fungal infections) and opportunistic infections have occurred in
patients with hematological malignancies treated with BRUKINSA.
Grade 3 or higher infections occurred in 26% of patients, most
commonly pneumonia (7.9%), with fatal infections occurring in 3.2%
of patients. Infections due to hepatitis B virus (HBV) reactivation
have occurred.
Consider prophylaxis for herpes simplex virus, pneumocystis
jirovecii pneumonia, and other infections according to standard of
care in patients who are at increased risk for infections. Monitor
and evaluate patients for fever or other signs and symptoms of
infection and treat appropriately.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (21%),
thrombocytopenia (8%) and anemia (8%) based on laboratory
measurements, developed in patients treated with BRUKINSA. Grade 4
neutropenia occurred in 10% of patients, and Grade 4
thrombocytopenia occurred in 2.5% of patients.
Monitor complete blood counts regularly during treatment and
interrupt treatment, reduce the dose, or discontinue treatment as
warranted. Treat using growth factor or transfusions, as
needed.
Second Primary Malignancies
Second primary malignancies, including non-skin carcinoma, have
occurred in 14% of patients treated with BRUKINSA. The most
frequent second primary malignancy was non-melanoma skin cancers
(8%), followed by other solid tumors in 7% of the patients
(including melanoma in 1% of patients) and hematologic malignancies
(0.7%). Advise patients to use sun protection and monitor patients
for the development of second primary malignancies.
Cardiac Arrhythmias
Serious cardiac arrhythmias have occurred in patients treated
with BRUKINSA. Atrial fibrillation and atrial flutter were reported
in 4.4% patients treated with BRUKINSA, including Grade 3 or higher
cases in 1.9% of patients. Patients with cardiac risk factors,
hypertension, and acute infections may be at increased risk. Grade
3 or higher ventricular arrhythmias were reported in 0.3% of
patients.
Monitor for signs and symptoms of cardiac arrhythmias (e.g.,
palpitations, dizziness, syncope, dyspnea, chest discomfort),
manage appropriately, and consider the risks and benefits of
continued BRUKINSA treatment.
Hepatotoxicity, Including Drug-Induced Liver Injury
Hepatotoxicity, including severe, life-threatening, and
potentially fatal cases of drug-induced liver injury (DILI), has
occurred in patients treated with Bruton tyrosine kinase
inhibitors, including BRUKINSA.
Evaluate bilirubin and transaminases at baseline and throughout
treatment with BRUKINSA. For patients who develop abnormal liver
tests after BRUKINSA, monitor more frequently for liver test
abnormalities and clinical signs and symptoms of hepatic toxicity.
If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI,
discontinue BRUKINSA.
Embryo-Fetal Toxicity
Based on findings in animals, BRUKINSA can cause fetal harm when
administered to a pregnant woman. Administration of zanubrutinib to
pregnant rats during the period of organogenesis caused
embryo-fetal toxicity, including malformations at exposures that
were 5 times higher than those reported in patients at the
recommended dose of 160 mg twice daily. Advise women to avoid
becoming pregnant while taking BRUKINSA and for 1 week after the
last dose. Advise men to avoid fathering a child during treatment
and for 1 week after the last dose. If this drug is used during
pregnancy, or if the patient becomes pregnant while taking this
drug, the patient should be apprised of the potential hazard to a
fetus.
Adverse Reactions
The most common adverse reactions (≥30%), including laboratory
abnormalities, in patients who received BRUKINSA (N=1729) are
decreased neutrophil count (51%), decreased platelet count (41%),
upper respiratory tract infection (38%), hemorrhage (32%), and
musculoskeletal pain (31%).
Drug Interactions
CYP3A Inhibitors: When BRUKINSA is co-administered with a
strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily.
For coadministration with a moderate CYP3A inhibitor, reduce
BRUKINSA dose to 80 mg twice daily.
CYP3A Inducers: Avoid coadministration with strong or
moderate CYP3A inducers. Dose adjustment may be recommended with
moderate CYP3A inducers.
Specific Populations
Hepatic Impairment: The recommended dose of BRUKINSA for
patients with severe hepatic impairment is 80 mg orally twice
daily.
Please see full U.S. Prescribing Information
including U.S. Patient Information.
This information is intended for a global audience. Product
indications vary by region.
About BeiGene
BeiGene is a global oncology company that is discovering and
developing innovative treatments that are more affordable and
accessible to cancer patients worldwide. With a broad portfolio, we
are expediting development of our diverse pipeline of novel
therapeutics through our internal capabilities and collaborations.
We are committed to radically improving access to medicines for far
more patients who need them. Our growing global team of more than
10,000 colleagues spans five continents. To learn more about
BeiGene, please visit www.beigene.com and follow us on LinkedIn, X
(formerly known as Twitter), and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
and other federal securities laws, including statements regarding
the efficacy and tolerability of zanubrutinib in combination with a
BCL2 inhibitor for high-risk CLL patients; BRUKINSA’s ability to
complement BCL2 therapies to achieve clinical response in high-risk
CLL patients; the future progression of the SEQUOIA trial; and
BeiGene’s plans, commitments, aspirations, and goals under the
heading “About BeiGene.” Actual results may differ materially from
those indicated in the forward-looking statements as a result of
various important factors, including BeiGene’s ability to
demonstrate the efficacy and safety of its drug candidates; the
clinical results for its drug candidates, which may not support
further development or marketing approval; actions of regulatory
agencies, which may affect the initiation, timing, and progress of
clinical trials and marketing approval; BeiGene’s ability to
achieve commercial success for its marketed medicines and drug
candidates, if approved; BeiGene’s ability to obtain and maintain
protection of intellectual property for its medicines and
technology; BeiGene’s reliance on third parties to conduct drug
development, manufacturing, commercialization, and other services;
BeiGene’s limited experience in obtaining regulatory approvals and
commercializing pharmaceutical products; BeiGene’s ability to
obtain additional funding for operations and to complete the
development of its drug candidates and achieve and maintain
profitability; and those risks more fully discussed in the section
entitled “Risk Factors” in BeiGene’s most recent quarterly report
on Form 10-Q, as well as discussions of potential risks,
uncertainties, and other important factors in BeiGene’s subsequent
filings with the U.S. Securities and Exchange Commission. All
information in this press release is as of the date of this press
release, and BeiGene undertakes no duty to update such information
unless required by law.
To access BeiGene media resources, please visit our News
& Media site.
_____________________ 1 Tam CS, Giannopoulos K, Jurczak W, et
al. SEQUOIA: Results of a Phase 3 Randomized Study of Zanubrutinib
versus Bendamustine + Rituximab (BR) in Patients with
Treatment-Naïve (TN) Chronic Lymphocytic Leukemia/Small Lymphocytic
Lymphoma (CLL/SLL), Blood. 2021;138(Supplement 1, p396)
doi:10.1182/blood-2021-148457 2 Tam CS, Brown JR, Kahl BS, et al.
Zanubrutinib versus bendamustine and rituximab in untreated chronic
lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a
randomised, controlled, phase 3 trial. Lancet Oncology.
2022;23(8):1031-1043. doi:10.1016/S1470-2045(22)00293-5.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240614058364/en/
Investor Contact: Liza Heapes +1 857-302-5663
ir@beigene.com
Media Contacts: Kyle Blankenship +1 667-351-5176
media@beigene.com
Maryline Iva +41 61 685 2090
BeiGene (NASDAQ:BGNE)
Historical Stock Chart
From May 2024 to Jun 2024
BeiGene (NASDAQ:BGNE)
Historical Stock Chart
From Jun 2023 to Jun 2024