Key Highlights

• The FDA accepted and granted Priority Review to BeOne Medicines' supplemental NDA for BRUKINSA plus rituximab in first-line mantle cell lymphoma

• Phase 3 MANGROVE data showed a 43% reduction in the risk of progression or death versus bendamustine plus rituximab

• If approved, BRUKINSA plus rituximab would be the first chemotherapy-free BTK inhibitor-based regimen for previously untreated MCL

• Full MANGROVE results will be presented during the Plenary Scientific Session at the 68th ASH Annual Meeting on December 13, 2026

BeOne Medicines Ltd.(NASDAQ:ONC), a global oncology company, announced on November 4, 2026, that the U.S. Food and Drug Administration has accepted and granted Priority Review to its supplemental New Drug Application for BRUKINSA (zanubrutinib) in combination with rituximab for adult patients with previously untreated mantle cell lymphoma. The FDA's Priority Review Designation is reserved for medicines that may offer significant improvements over available therapies.

MANGROVE Trial Results

The sNDA is supported by data from the Phase 3 MANGROVE study (BGB-3111-306), a global, randomized trial that evaluated BRUKINSA plus rituximab against bendamustine plus rituximab (BR) in adult patients with previously untreated mantle cell lymphoma. The trial enrolled 510 patients across 157 active sites worldwide and is described as the first Phase 3 study to evaluate a chemotherapy-free, BTK inhibitor-based regimen against standard chemoimmunotherapy in the frontline MCL setting.

In the trial, BRUKINSA plus rituximab reduced the risk of progression or death by 43% versus BR, achieving a hazard ratio of 0.57 with a 95% confidence interval of 0.43 to 0.76 and a p-value of less than 0.0001. The result met the trial's primary endpoint of progression-free survival as assessed by an independent review committee. The safety profile of the combination was consistent with the known safety profiles of both medicines, with no new safety signals identified.

Trial Design and Treatment Arms

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 was progression-free survival assessed by an independent review committee, with overall survival as a key secondary endpoint.

Additional secondary endpoints include investigator-assessed PFS, overall response rate, duration of response, patient-reported outcomes, and safety. Full results from the MANGROVE study will be presented during the Plenary Scientific Session at the 68th American Society of Hematology Annual Meeting on December 13, 2026.

Global Regulatory Submissions

Beyond the FDA filing, a supplemental new drug application for BRUKINSA for the treatment of MCL has also been submitted to the European Medicines Agency and accepted by the Center for Drug Evaluation of the China National Medical Products Administration. BRUKINSA is currently approved in the U.S. for adult patients with relapsed or refractory MCL, as well as for chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström's macroglobulinemia, relapsed or refractory marginal zone lymphoma, and relapsed or refractory follicular lymphoma.

BeOne Medicines' Chief Medical Officer for Hematology, Amit Agarwal, noted that chemoimmunotherapy remains a mainstay of frontline MCL treatment despite the toxicity burden it carries, and characterized the FDA's acceptance as bringing the company closer to a chemotherapy-free option for patients.

The Path Forward

The FDA's Priority Review designation for BRUKINSA in combination with rituximab for first-line mantle cell lymphoma marks a potentially significant development in the treatment landscape for this hematologic malignancy. If approved, the regimen would become the first and only chemotherapy-free BTK inhibitor-based option for previously untreated MCL patients. The upcoming Plenary Scientific Session presentation at ASH in December 2026 will provide the full dataset from MANGROVE, which the broader oncology community will evaluate as the regulatory review proceeds.