BeOne Medicines Receives FDA Priority Review for BRUKINSA Plus Rituximab in Previously Untreated Mantle Cell Lymphoma
BeOne Medicines Ltd., a global oncology company focused on developing innovative cancer treatments, has announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to its supplemental New Drug Application (sNDA) for BRUKINSA® (zanubrutinib) in combination with rituximab for the treatment of adults with previously untreated mantle cell lymphoma (MCL).
The regulatory submission is supported by positive findings from the pivotal Phase 3 MANGROVE clinical trial, which evaluated the chemotherapy-free combination of BRUKINSA and rituximab against standard bendamustine plus rituximab (BR) chemoimmunotherapy. Results demonstrated that the BRUKINSA-based regimen significantly reduced the risk of disease progression or death compared with the established treatment combination.
The FDA’s decision to grant Priority Review represents an important regulatory milestone for BeOne Medicines as it seeks to expand the use of BRUKINSA into the frontline treatment setting for patients with mantle cell lymphoma. If approved, the combination could provide an additional treatment option for adults newly diagnosed with this challenging blood cancer, potentially reducing the need for conventional chemotherapy.
The company stated that the full results from the MANGROVE study will be presented during the Plenary Scientific Session at the 68th Annual Meeting of the American Society of Hematology (ASH 2026) on December 13, 2026. The presentation is expected to provide further insights into the efficacy and safety of the combination and its potential role in changing the frontline treatment landscape for MCL.
FDA Priority Review Advances BRUKINSA’s Frontline Development
The acceptance of the sNDA and assignment of Priority Review mark a significant step in BeOne Medicines’ efforts to broaden the clinical application of BRUKINSA. The application seeks approval of zanubrutinib in combination with rituximab for adults with previously untreated mantle cell lymphoma, an indication that represents an important area of unmet medical need.
Mantle cell lymphoma is a relatively uncommon type of non-Hodgkin lymphoma that develops from malignant B lymphocytes, a type of white blood cell involved in the immune system. The disease is generally considered an aggressive form of lymphoma, although its clinical course can vary considerably among patients.
MCL is often characterized by a pattern of initial treatment response followed by eventual relapse or disease progression. While available therapies have improved outcomes, selecting an effective frontline treatment remains important because patients may require multiple subsequent lines of therapy throughout the course of their disease.
Historically, chemoimmunotherapy combinations have played a central role in the initial management of MCL. These regimens combine conventional chemotherapy agents with targeted immune-based treatments to eliminate malignant cells. However, chemotherapy can be associated with substantial toxicity, including suppression of bone marrow function, increased infection risk, fatigue, and other treatment-related complications.
The development of chemotherapy-free treatment combinations is therefore an important focus of ongoing research in hematologic malignancies.
BRUKINSA, a Bruton tyrosine kinase (BTK) inhibitor, is designed to interfere with signaling pathways that contribute to the survival, growth, and proliferation of malignant B cells. Its combination with rituximab, an anti-CD20 monoclonal antibody, represents a targeted approach intended to attack lymphoma cells through complementary mechanisms.
The FDA’s Priority Review designation is expected to support an expedited regulatory evaluation of the application compared with the standard review pathway. This development brings BeOne Medicines closer to potentially making the combination available to patients with previously untreated MCL in the United States.
MANGROVE Phase 3 Trial Demonstrates Significant Reduction in Disease Progression Risk
The regulatory application is based on findings from MANGROVE (BGB-3111-306), a global, randomized, Phase 3 clinical trial designed to compare BRUKINSA plus rituximab with bendamustine plus rituximab in adults with previously untreated mantle cell lymphoma.
The study evaluated whether the chemotherapy-free combination could improve clinical outcomes compared with a commonly used chemoimmunotherapy regimen.
According to the reported results, treatment with BRUKINSA plus rituximab reduced the risk of disease progression or death by 43% compared with bendamustine plus rituximab.
The primary endpoint of the study was progression-free survival (PFS), assessed by an independent review committee. The trial met this primary endpoint, demonstrating a statistically significant improvement in PFS for patients receiving the BRUKINSA-based combination.
The reported hazard ratio was 0.57, with a 95% confidence interval of 0.43–0.76 and a p-value of less than 0.0001.
These results indicate a substantial reduction in the risk of disease progression or death among patients treated with BRUKINSA plus rituximab compared with those receiving the standard chemoimmunotherapy combination.
Progression-free survival is an important clinical endpoint in lymphoma trials because it measures the length of time patients live without their disease worsening or experiencing another progression-related event. Improvements in PFS can provide meaningful evidence of a treatment’s ability to control cancer over time.
The statistical significance reported in MANGROVE supports the potential clinical benefit of the investigational combination in the frontline MCL setting.
Importantly, the study compared the targeted combination directly with bendamustine plus rituximab, providing evidence against an established treatment approach rather than relying solely on comparisons with historical clinical outcomes.
The findings support further consideration of BRUKINSA plus rituximab as a potential chemotherapy-free option for patients beginning treatment for mantle cell lymphoma.
Chemotherapy-Free Combination Could Address Treatment Challenges
One of the key objectives of the MANGROVE study was to determine whether a targeted treatment combination could deliver improved disease control while avoiding the toxicity associated with conventional chemotherapy.
Bendamustine plus rituximab has been an established treatment option for patients with several B-cell malignancies, including mantle cell lymphoma. However, bendamustine is a cytotoxic chemotherapy agent that can affect both malignant and healthy dividing cells.
Treatment-related toxicities associated with chemotherapy may create additional challenges for patients, particularly those who are older or have other medical conditions that complicate cancer treatment.
By contrast, BRUKINSA plus rituximab combines two targeted treatment approaches.
Zanubrutinib works by inhibiting BTK, an enzyme that plays a central role in B-cell receptor signaling. This signaling pathway is important for the development, activation, proliferation, and survival of B cells. In certain B-cell malignancies, abnormal signaling can contribute to the continued growth and survival of cancer cells.
By blocking BTK activity, zanubrutinib is designed to disrupt these signaling processes and inhibit malignant B-cell activity.
Rituximab targets the CD20 protein expressed on the surface of B cells. Binding to CD20 helps trigger immune-mediated mechanisms that contribute to the destruction of targeted B cells.
Combining zanubrutinib with rituximab therefore provides two complementary mechanisms of action against malignant B cells.
The positive MANGROVE results suggest that this chemotherapy-free strategy may offer improved disease control compared with bendamustine plus rituximab. Further evaluation of the complete clinical dataset will be important for understanding the magnitude and durability of treatment benefit, as well as the overall impact on patients’ quality of life.
BeOne Highlights Potential of BRUKINSA-Based Treatment Strategy
Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, at BeOne Medicines, emphasized the importance of the FDA’s decision and the potential of the combination to provide a new approach for patients with newly diagnosed mantle cell lymphoma.
“In newly diagnosed mantle cell lymphoma, chemoimmunotherapy remains a mainstay of frontline treatment despite the toxicity burden it carries. The FDA’s acceptance of our application brings us closer to a chemotherapy-free, BRUKINSA-based option that significantly reduces the risk of disease progression or death,” said Dr. Agarwal.
He further highlighted the treatment’s ability to generate deeper and more powerful responses as an important factor supporting the development of a chemotherapy-free approach.
“BRUKINSA’s ability to drive deeper, more powerful responses is what makes a chemotherapy-free approach now possible. We look forward to working closely with the FDA to make our foundational BTK inhibitor available to patients as quickly as possible,” he added.
The company’s regulatory strategy reflects its efforts to build on the established clinical development and commercial presence of BRUKINSA while expanding its potential use across additional patient populations.
The FDA’s Priority Review decision provides an opportunity for the company to pursue a potentially broader role for zanubrutinib in the treatment of mantle cell lymphoma.
Additional Regulatory Submissions Underway in Europe and China
Alongside the U.S. regulatory submission, BeOne Medicines is pursuing additional regulatory reviews for BRUKINSA in combination with rituximab for mantle cell lymphoma in other major markets.
The company has submitted a supplemental application to the European Medicines Agency (EMA). In China, the relevant application has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA).
These submissions demonstrate BeOne Medicines’ intention to pursue broader international access to the BRUKINSA-based combination, subject to regulatory review and approval in individual markets.
The simultaneous regulatory activities in the United States, Europe, and China represent an important component of the company’s global oncology development strategy.
Regulatory decisions in these markets could potentially expand treatment availability for patients with previously untreated MCL and provide physicians with additional options for managing the disease.
BRUKINSA’s Established Regulatory Presence Across B-Cell Malignancies
BRUKINSA is an orally administered BTK inhibitor developed by BeOne Medicines for the treatment of several B-cell malignancies.
In the United States, BRUKINSA is currently approved for adults with multiple hematologic cancer indications, including:
- Relapsed or refractory mantle cell lymphoma (MCL).
- Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
- Waldenström’s macroglobulinemia (WM).
- Relapsed or refractory marginal zone lymphoma (MZL).
- Relapsed or refractory follicular lymphoma (FL).
The existing approval for relapsed or refractory MCL provides an established regulatory foundation for the company’s efforts to expand zanubrutinib into the previously untreated disease setting.
An approval for the proposed combination with rituximab would represent a further expansion of BRUKINSA’s role in mantle cell lymphoma, potentially bringing the therapy into an earlier stage of treatment.
The broader clinical development program also reflects the importance of BTK inhibition as a therapeutic strategy across B-cell cancers, where abnormal B-cell signaling contributes to disease development and progression.
ASH 2026 Presentation to Provide Further Insights Into MANGROVE Results
The upcoming presentation of the full MANGROVE clinical findings at the 68th American Society of Hematology Annual Meeting will be an important opportunity for the hematology community to evaluate the study results in greater detail.
The presentation is scheduled for December 13, 2026, during the meeting’s Plenary Scientific Session.
The complete dataset is expected to provide additional context regarding the clinical performance of BRUKINSA plus rituximab, including the efficacy and safety findings supporting the regulatory submission.
For BeOne Medicines, the FDA’s acceptance of the sNDA and Priority Review designation represent important milestones in advancing its frontline MCL strategy.
The 43% reduction in the risk of disease progression or death observed in the Phase 3 MANGROVE study provides a strong clinical basis for continued regulatory evaluation of the chemotherapy-free regimen.
As regulatory reviews progress in the United States, Europe, and China, the company aims to expand access to targeted treatment approaches for patients with B-cell malignancies.
If approved for previously untreated mantle cell lymphoma, BRUKINSA plus rituximab could offer physicians an additional frontline treatment option and potentially reduce reliance on conventional chemoimmunotherapy. The forthcoming ASH 2026 presentation and ongoing regulatory assessments will be important in determining the treatment’s future role in the management of this challenging hematologic cancer.
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 157 active sites worldwide and is the first Phase 3 trial to evaluate a chemotherapy-free, BTK inhibitor-based regimen against standard chemoimmunotherapy with BR in the frontline MCL setting.
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 310,000 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.