BeOne Medicines Announces Topline Results From Its Phase 3 MANGROVE Study Of Foundational BTK Inhibitor Brukinsa Plus Rituximab In Adult Pat

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 rituximab 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 MCL 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.