BeOne Medicines has announced positive topline results from its pivotal Phase 3 MANGROVE study evaluating Brukinsa (zanubrutinib) in combination with rituximab for the treatment of adult patients with previously untreated Mantle Cell Lymphoma (MCL). The study met its primary endpoint, demonstrating that the chemotherapy-free regimen significantly improved Progression-Free Survival (PFS) compared with the current standard treatment of Bendamustine plus Rituximab (BR).

The MANGROVE trial is the first global, randomised Phase 3 study to compare a Bruton Tyrosine Kinase (BTK) inhibitor-based chemotherapy-free regimen against standard chemoimmunotherapy in the frontline treatment of mantle cell lymphoma. The findings further strengthen the clinical evidence supporting Brukinsa as a foundational therapy for B-cell malignancies.

According to the prespecified interim analysis, patients receiving Brukinsa plus rituximab experienced a 43 percent reduction in the risk of disease progression or death compared with those treated with bendamustine plus rituximab. The study also introduced a chemotherapy-free and rituximab maintenance-free treatment approach, potentially sparing patients nearly two years of infusion-based therapy.

The safety profile of Brukinsa in combination with rituximab remained consistent with the known safety characteristics of both medicines and no new safety signals were identified during the study. While overall survival, a key secondary endpoint, remains immature at this stage of the analysis, the company reported a strong positive trend favouring the Brukinsa-based regimen. Final overall survival data will be assessed in the study's concluding analysis.

Commenting on the results, Dr. Amit Agarwal, Chief Medical Officer, Haematology, BeOne Medicines, said that chemotherapy has long been the standard first-line treatment for newly diagnosed mantle cell lymphoma. He noted that the MANGROVE study demonstrates for the first time that a chemotherapy-free combination of Brukinsa and rituximab can deliver significant improvements in progression-free survival while reducing the treatment burden associated with frequent infusions. He added that the findings reinforce Brukinsa's role as a foundational therapy capable of redefining frontline treatment across B-cell malignancies.

Mantle cell lymphoma is a rare and aggressive form of B-cell non-Hodgkin lymphoma that primarily affects older adults, many of whom have additional health conditions that influence treatment choices. Standard chemoimmunotherapy regimens, such as bendamustine plus rituximab, are associated with well-recognised side effects, including myelosuppression, prolonged immune suppression, increased infection risk and cumulative toxicity, making treatment particularly challenging for elderly patients.

Unlike previous efforts that combined BTK inhibitors with chemotherapy, the MANGROVE trial evaluated whether chemotherapy could be eliminated altogether while maintaining durable disease control. The study enrolled 510 patients across 176 sites worldwide in a randomised, open-label Phase 3 design.

Patients in the experimental arm received Brukinsa at a dose of 160 mg orally twice daily along with rituximab during the induction phase, followed by Brukinsa monotherapy until disease progression or intolerance. Patients in the control arm received six cycles of bendamustine plus rituximab. In addition to progression-free survival, the trial is evaluating overall survival, overall response rate, duration of response, patient-reported outcomes and safety.

BeOne Medicines said the complete data from the MANGROVE study will be presented at an upcoming scientific meeting. The company is also engaged in discussions with global regulatory authorities and plans to submit regulatory applications for the new indication during the second half of 2026.

Brukinsa is a next-generation BTK inhibitor designed to provide complete and sustained BTK inhibition through optimised pharmacokinetics and high selectivity. The medicine is currently approved in more than 80 countries and has been used to treat over 290,000 patients worldwide. Its global clinical development programme includes more than 8,000 patients enrolled across over 45 clinical trials in more than 30 countries and regions.

BeOne Medicines continues to expand its oncology portfolio across haematological malignancies and solid tumours, leveraging its research capabilities and global collaborations to develop innovative cancer therapies.