Foundational BTKi BRUKINSA plus rituximab reduced the risk of progression or
death by 43% versus bendamustine plus rituximab (HR=0.57; p<0.0001), meeting
the primary endpoint of PFS
MANGROVE is the first Phase 3 trial to advance a new chemotherapy-free standard
in frontline MCL, potentially allowing patients freedom from the burden of years of
infusions
Full results from MANGROVE, including efficacy and safety, will be presented at an
upcoming medical meeting; global regulatory submissions are planned for 2H 2026
SAN CARLOS, Calif.--(BUSINESS WIRE)-- BeOne Medicines Ltd. (Nasdaq: ONC;
HKEX: 06160; SSE: 688235), a global oncology company, today announced positive
topline results from the Phase 3 MANGROVE study (BGB-3111-306; NCT04002297)
evaluating foundational BTK inhibitor BRUKINSA ® (zanubrutinib) plus rituxima8b
versus bendamustine plus rituximab (BR) in adult patients with previously untreated
mantle cell lymphoma (MCL). MANGROVE is the first Phase 3, global, randomized
trial to evaluate a BTK inhibitor-based chemotherapy-free regimen against standard
chemoimmunotherapy in this setting. This pivotal Phase 3 trial builds on the
established clinical evidence for BRUKINSA in MCL.
Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne
Medicines, said:
“For patients with newly diagnosed MCL, chemotherapy is currently the default.
MANGROVE demonstrates for the first time that BRUKINSA plus rituximab, a
chemotherapy-free regimen, can deliver unprecedented improvements in
progression-free survival, potentially redefining the treatment paradigm globally. We
believe it would be very meaningful for patients to be free from the burden of
frequent infusions. This is what it means to state that BRUKINSA is foundational:
another study where it anchors frontline therapy and extends its leadership across B-
cell malignancies.”
Topline results with practice-changing potential
For this prespecified interim analysis, MANGROVE met its primary endpoint of
progression-free survival (PFS), demonstrating a highly statistically significant and
clinically meaningful improvement for BRUKINSA plus rituximab versus BR, as
assessed by an independent review committee (IRC). This is the first Phase 3 study
of its kind to employ a chemotherapy-free, rituximab maintenance-free approach in
first-line MCL, sparing patients approximately two years of infusions. This
BRUKINSA-based, chemotherapy-free regimen led to a 43% reduction in the risk of
progression or death (HR=0.57; [95% CI, 0.43, 0.76]; p<0.0001). The safety profile of
BRUKINSA plus rituximab was consistent with the known safety profile of both
medicines, with no new safety signals identified. Overall survival (OS), a key
secondary endpoint, was immature at the time of this analysis; however, a strong
trend in favor of BRUKINSA plus rituximab was observed. OS will be tested as part
of the final analysis.
Full results from MANGROVE will be shared at an upcoming medical meeting. The
Company is in discussions with global regulatory authorities with planned
submissions in 2H 2026.
Why a chemotherapy-free approach is needed in MCL
Mantle cell lymphoma is a rare and typically aggressive (fast-growing) type of B-cell
non-Hodgkin lymphoma. 1 It predominantly affects older adults, who often have
comorbidities that can influence treatment decisions and how well they can tolerate
therapies. 2 Frontline care has long relied on chemoimmunotherapy such as BR. 3
Chemoimmunotherapy carries well-documented burdens, including
myelosuppression, prolonged immune suppression and heightened infection risk,
and cumulative toxicity that can be especially difficult for older patients. 4
Efforts to improve frontline outcomes in Brukinsa Mantle Cell Lymphoma with BTK
inhibitors have largely focused on adding them to chemotherapy rather than
replacing it. 5 MANGROVE takes a different approach, by evaluating whether a
chemotherapy-free regimen of BRUKINSA plus rituximab can deliver durable
disease control while sparing patients the burden of upfront chemotherapy. This
approach seeks to advance longstanding efficacy and tolerability limitations of first-
line care.
About MANGROVE
MANGROVE is a global, randomized, open-label Phase 3 trial evaluating
BRUKINSA plus rituximab versus bendamustine plus rituximab in adult patients with
previously untreated mantle cell lymphoma. The trial enrolled 510 patients across
176 sites worldwide.
In the experimental arm, patients received BRUKINSA at 160 mg orally twice daily
plus rituximab during the initial treatment period, followed by BRUKINSA
monotherapy until disease progression or intolerance. In the control arm, patients
received bendamustine plus rituximab for six cycles. The primary endpoint is PFS
assessed by IRC. Overall survival is a key secondary endpoint for the study. Other
secondary endpoints include investigator-assessed PFS, overall response rate
(ORR), duration of response (DOR), patient-reported outcomes, and safety.
About BRUKINSA® (zanubrutinib)
BRUKINSA is a next-generation Bruton tyrosine kinase (BTK) inhibitor designed to
deliver complete and sustained BTK inhibition, enabled by optimized
pharmacokinetics, including bioavailability, half-life, and selectivity, resulting in
consistent target coverage in disease-relevant tissues.
BRUKINSA is the foundational BTK inhibitor and the first and only to demonstrate
progression-free survival superiority over another BTK inhibitor in a Phase 3 study,
setting a new benchmark for efficacy in the class. With the broadest label globally, it
is also the only BTK inhibitor that offers the convenience of once- or twice-daily
dosing to support individualized treatment.
The global BRUKINSA clinical development program spans more than 8,000
patients across over 45 trials in 30+ countries and regions. Approved in more than
80 markets, BRUKINSA has been used to treat over 290,000 patients worldwide,
reflecting its rapidly expanding role as a standard of care across B-cell malignancies.
Select Important Safety Information for BRUKINSA
Serious adverse reactions, including fatal events, have occurred with BRUKINSA,
including hemorrhage, infections, cytopenias, second primary malignancies, cardiac
arrhythmias, and hepatotoxicity (including drug-induced liver injury).
In the pooled safety population (N=1729), the most common adverse reactions
(≥30%), including laboratory abnormalities, in patients who received BRUKINSA
were neutrophil count decreased (51%), platelet count decreased (41%), upper
respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain
(31%).
Please see full U.S. Prescribing Information including U.S. Patient Information.
About BeOne
BeOne Medicines is a global oncology company that is discovering and developing
innovative treatments for cancer patients worldwide. With a portfolio spanning
hematology and solid tumors, BeOne is expediting development of its diverse
pipeline of novel therapeutics through its internal capabilities and collaborations. The
Company has a growing global team spanning six continents who are driven by
scientific excellence and exceptional speed to reach more patients than ever before.
To learn more about BeOne, please visit www.beonemedicines.com and follow us
on LinkedIn, X, Facebook and Instagram.
Forward-Looking Statement
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 potential benefits of BRUKINSA plus rituximab as
a chemotherapy-free regimen in adult patients with previously untreated MCL; the
foundational potential of BRUKINSA to anchor frontline therapy on its own and
extend its leadership across B-cell malignancies; the timing of clinical and regulatory
developments and data readouts; and BeOne’s plans, commitments, aspirations,
and goals under the heading “About BeOne.” Actual results may differ materially
from those indicated in the forward-looking statements as a result of various
important factors, including BeOne’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; BeOne’s ability to achieve commercial success for its marketed medicines
and drug candidates, if approved; BeOne’s ability to obtain and maintain protection
of intellectual property for its medicines and technology; BeOne’s reliance on third
parties to conduct drug development, manufacturing, commercialization, and other
services; BeOne’s limited experience in obtaining regulatory approvals and
commercializing pharmaceutical products and its 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 BeOne’s most recent quarterly report on Form 10-Q, as well as
discussions of potential risks, uncertainties, and other important factors in BeOne’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 BeOne
undertakes no duty to update such information unless required by law.
To access BeOne media resources, please visit our Newsroom.
1 National Cancer Institute. Mantle cell lymphoma. NCI Dictionary of Cancer Terms. Accessed June 16, 2026. https://www.cancer.gov/publications/dictionaries/cancer-
terms/def/mantle-cell-lymphoma.
2 National Cancer Institute. Mantle Cell Lymphoma Treatment (PDQ®)–Health Professional Version. Accessed June 16, 2026.
3 Tix T, Kumar A, Eyre TA, Dreyling M. Modern management of mantle cell lymphoma. J Clin Oncol. 2026;46:e517468.
4 Blayney DW, Schwartzberg L. Chemotherapyinduced neutropenia and emerging agents for prevention and treatment: a review. Cancer Treat Rev. 2022;109:102427.
5 Noor WD, Cheah CY. Recent advances and future directions in newly diagnosed mantle cell lymphoma. Expert Opin Pharmacother. 2025;26(13):1415-1432.
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