Zanubrutinib Combination Receives FDA Priority Review Following Positive Phase 3 MANGROVE Results
Clinical Summary:
-
Regulatory Update: The US Food and Drug Administration (FDA) has accepted and granted Priority Review to the supplemental new drug application for zanubrutinib plus rituximab in adults with previously untreated mantle cell lymphoma (MCL).
-
Key Outcomes: The application was supported by results from the phase 3 MANGROVE trial, in which zanubrutinib plus rituximab significantly improved progression-free survival compared with bendamustine plus rituximab, reducing the risk of disease progression or death by 43%. No new safety signals were identified.
-
Clinical Relevance: If approved, zanubrutinib plus rituximab would introduce a chemotherapy-free, Bruton tyrosine kinase (BTK) inhibitor-based treatment option for previously untreated MCL, potentially reducing reliance on conventional chemoimmunotherapy in the first-line setting.
The US Food and Drug Administration (FDA) has accepted and granted Priority Review to the supplemental new drug application for zanubrutinib (Brukinsa; BeOne Medicines) in combination with rituximab for adult patients with previously untreated mantle cell lymphoma (MCL), following positive progression-free survival (PFS) results from the phase 3 MANGROVE trial.
The November 4, 2026, regulatory decision advances a potential chemotherapy-free, Bruton tyrosine kinase (BTK) inhibitor-based treatment option for patients with newly diagnosed MCL.
In this open-label trial, 510 patients were enrolled across 157 active clinical sites worldwide to receive either 160 mg of twice daily zanubrutinib in combination with rituximab during the initial treatment period, followed by zanubrutinib monotherapy until disease progression or intolerance or bendamustine plus rituximab for 6 cycles.
The primary end point was PFS, assessed by independent review. Key secondary end points included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response, patient-reported outcomes, and safety.
At analysis, zanubrutinib plus rituximab significantly improved PFS compared with bendamustine plus rituximab, reducing the risk of disease progression or death by 43% (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43 to 0.76; P < .0001), meeting the trial's primary end point.
The safety profile of zanubrutinib plus rituximab was consistent with the known safety profiles of the individual agents, with no new safety signals identified.
Detailed efficacy and safety findings, including median PFS, OS, ORR, and adverse event rates from MANGROVE, were not provided in the announcement. Full results from MANGROVE are scheduled for presentation during the Plenary Scientific Session at the 68th American Society of Hematology (ASH) Annual Meeting on December 13, 2026.
Zanubrutinib is currently FDA approved for adults with relapsed or refractory MCL, as well as chronic lymphocytic leukemia or small lymphocytic lymphoma, Waldenström macroglobulinemia, relapsed or refractory marginal zone lymphoma, and relapsed or refractory follicular lymphoma.
If approved, zanubrutinib plus rituximab would represent a chemotherapy-free BTK inhibitor-based regimen for adults with previously untreated MCL.
In addition to the FDA submission, BeOne Medicines has submitted a supplemental application to the European Medicines Agency and received acceptance of its application from China's National Medical Products Administration Center for Drug Evaluation.
Source:
BeOne Medicines. US FDA grants priority review to BeOne Medicines’ BRUKINSA combination in first-line mantle cell lymphoma. Accessed on: November 4, 2026. https://ir.beonemedicines.com/news/us-fda-grants-priority-review-to-beone-medicines-brukinsa-combination-in-first-line-mantle-cell-lymphoma/b074b7a8-a9b4-48ce-b5ca-4b2c63fedece
