BeOne’s BRUKINSA Plus Rituximab Cuts Progression Risk by 43% in First-Line Mantle Cell Lymphoma Phase 3 Trial

BeOne Medicines has reported positive topline results from the global Phase 3 MANGROVE trial (NCT04002297), demonstrating that BRUKINSA (zanubrutinib) plus rituximab significantly prolonged progression-free survival (PFS) compared with the current chemoimmunotherapy standard of bendamustine plus rituximab (BR) in adults with previously untreated mantle cell lymphoma (MCL). The findings support the first chemotherapy-free BTK inhibitor-based regimen to outperform frontline BR in a Phase 3 study and may reshape initial treatment for this aggressive B-cell malignancy.

At the prespecified interim analysis, the combination reduced the risk of disease progression or death by 43% versus BR (hazard ratio [HR] 0.57; 95% CI, 0.43–0.76; p<0.0001), meeting the trial’s primary endpoint of independently reviewed PFS.

Chemotherapy-free approach addresses an important unmet need

Mantle cell lymphoma is a rare, aggressive subtype of B-cell non-Hodgkin lymphoma that primarily affects older adults, many of whom have comorbidities that limit tolerance to intensive chemotherapy. Bendamustine plus rituximab remains a widely used frontline regimen but is associated with myelosuppression, prolonged immunosuppression, cumulative toxicity, and maintenance rituximab infusions.

BRUKINSA is a next-generation Bruton tyrosine kinase (BTK) inhibitor that provides sustained BTK inhibition through favorable pharmacokinetic properties and high selectivity. In MANGROVE, patients received BRUKINSA 160 mg orally twice daily with rituximab during induction, followed by BRUKINSA monotherapy until disease progression or intolerance, avoiding both chemotherapy and approximately two years of rituximab maintenance therapy.

 Phase 3 MANGROVE met its primary endpoint

MANGROVE is a global, randomized, open-label Phase 3 trial enrolling 510 patients across 176 sites worldwide. Participants were randomized to receive either BRUKINSA plus rituximab or six cycles of bendamustine plus rituximab.

The primary endpoint was PFS assessed by an independent review committee. Secondary endpoints include overall survival (OS), investigator-assessed PFS, overall response rate, duration of response, patient-reported outcomes, and safety.

Beyond the statistically significant PFS improvement, the safety profile of BRUKINSA plus rituximab remained consistent with the known safety profiles of both agents, and investigators reported no new safety signals. Overall survival data remain immature, although an early trend favored the BRUKINSA regimen. Formal OS analysis will occur at the final study readout.

Findings strengthen BRUKINSA’s frontline role

Commenting on the results, Amit Agarwal, MD, PhD, Chief Medical Officer, Hematology at BeOne Medicines, said the study demonstrates for the first time that a chemotherapy-free BRUKINSA-based regimen can outperform conventional frontline chemotherapy in newly diagnosed MCL. He noted that avoiding chemotherapy and prolonged maintenance infusions could meaningfully reduce treatment burden while improving disease control.

The results further expand BRUKINSA’s clinical evidence across B-cell malignancies and reinforce its role as a foundational BTK inhibitor in frontline therapy.

Regulatory submissions planned in 2026

BeOne Medicines plans to present the complete efficacy and safety results from MANGROVE at an upcoming medical meeting. The company is also preparing global regulatory submissions during the second half of 2026.

If approved, BRUKINSA plus rituximab could become the first Phase 3-validated chemotherapy-free frontline treatment for mantle cell lymphoma, offering patients an effective alternative to conventional chemoimmunotherapy while reducing long-term treatment burden.

Reference

BeOne Medicines Announces Positive Phase 3 Results for BRUKINSA in Frontline Mantle Cell Lymphoma – BeOne Medicines NASDAQ